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Biomedical subjects

M S Kramer

Publications and source records attributed to M S Kramer.

At least 19 recordsLinked to original sources

Maternal nutrition and spontaneous preterm birth.

Previous studies suggesting that maternal undernutrition increases the risk of preterm birth have suffered from several methodological shortcomings, including use of total gestational weight gain rather than net rate of gain in maternal tissue, inclusion of induced preterm deliveries, and error-prone gestational age measurements based solely on menstrual dates. The authors have attempted to overcome these shortcomings by investigating the potential etiologic roles of prepregnancy body mass index, net rate of maternal weight gain, height, and a number of other potential biological and sociodemographic determinants of spontaneous (i.e., noninduced) preterm birth in a cohort of 13,102 women with early ultrasound-confirmed gestational age who delivered at the Royal Victoria Hospital in Montreal, Quebec, Canada, between January 1, 1980 and March 31, 1989. Total weight gain, but not body mass index, was highly significantly associated with spontaneous preterm birth, averaging 14.6, 12.5, 9.9, and 9.1 kg, in women delivering at 37 or more, less than 37, less than 34, and less than 32 completed weeks, respectively. Although the relation persisted when weight gain was expressed as an overall rate, it disappeared when the analysis was based on net rate; mean net rates of gain were 0.28, 0.29, 0.27, and 0.27 kg/week, respectively. On the basis of multiple logistic regression analyses, significant determinants of birth at less than 37 weeks included maternal short stature; noncompletion of high school; unmarried status; smoking; diabetes; urinary tract infection within 2 weeks of delivery; prepregnancy hypertension; severe pregnancy-induced hypertension; and previous history of preterm delivery, low birth weight, or neonatal death. Most of these factors retained their significance for birth at less than 34 and less than 32 weeks. In fact, the effect of low maternal education was even stronger at these more severe "levels" of preterm birth. The authors conclude that prepregnancy weight-for-height and gestational weight gain are not important determinants of spontaneous preterm birth and that some previous studies have mistaken an effect of shortened gestation for its cause. Other biologic and social determinants, however, indicate priorities for future research and intervention.

Adult

Causal propositions in clinical research and practice.

The concept of causation is central to clinical research and practice. The health science literature on causality, largely contributed by epidemiologists, has examined the population-based question of whether an exposure can cause a given health outcome. Most of this literature has focused on criteria for assessing causality, rather than attempting to define it. Moreover, the population-based approach is rather distant from the individual persons in whom causes must act, which has led to different perspectives on causality among epidemiologists and health policy markers, on the one hand, and clinical practitioners and the lay public, on the other. We attempt to bridge the gap between these perspectives by defining three probabilistic causal propositions based on the locus (individual vs population) and time frame (past vs future outcome) to which they refer, beginning with the individual in whom a health outcome has already occurred ("retrodictive" causal propositions, i.e. It Did) and proceeding to "potential" causal propositions (It Can) for populations and "predictive" causal propositions (It Will) for individuals or populations. We conclude by showing how attention to these distinctions may help avoid common pitfalls that can impair clinical or public health decision-making.

Causality

Bias and 'overcall' in interpreting chest radiographs in young febrile children.

Few studies have examined the diagnostic validity of the examination physician's interpretation of chest radiographs in young febrile children, and none (to our knowledge) the extent to which the "official" (ie, the radiologist's) reading may be biased by access to the examining physician's reading and to other clinical information. The authors studied 287 consecutive chest radiographs obtained in 286 febrile children 3 to 24 months of age without chronic cardiopulmonary disease or known asthma who presented to a children's hospital emergency department between March 1989 and August 1990. The readings by treating pediatricians, official pediatric radiologists, and a "blind" pediatric radiologist were compared. Official radiologists had access to the treating pediatricians' readings and the clinical information provided on the radiography requisition. The blind radiologist knew only that each child was 3 to 24 months of age and febrile, and he was asked to judge the presence or absence of pneumonia. Using the blind radiologist's reading as the "gold standard" for judging validity of the treating physicians' and official radiologists' readings, sensitivity (.677 vs .647), specificity (.828 vs .849), positive predictive value (PPV, .537 vs .571), and kappa index (kappa, .462 vs .475) were quite similar. By contrast, agreement by the treating physicians was considerably higher with the official radiologists' readings as gold standard: sensitivity = .756, specificity = .922, PPV = .795, and kappa = .688. When the treating physician's reading was positive, the official radiologists' positivity rate was much higher than the blind radiologist's (74.4% vs 51.8%, P less than .005), sensitivity was high (.884) but specificity was low (.436), PPV was .663, and kappa was .326.(ABSTRACT TRUNCATED AT 250 WORDS)

Fever

Very low birth weight: a problematic cohort for epidemiologic studies of very small or immature neonates.

Despite widespread acceptance of the concept of very low birth weight (VLBW), i.e., birth weight of less than or equal to 1,500 g, VLBW infants represent an extremely heterogeneous group of newborns, including those with very immature gestational age and those who are more mature but extremely growth retarded. To demonstrate how use of the VLBW rubric can lead to confounding bias that is not only large in magnitude but impossible to control satisfactorily, the authors divided 640 consecutive live neonates born in the Royal Victoria Hospital, Montreal, Canada, from 1978 to 1987 into two overlapping groups: a VLBW cohort (birth weight, 500-1500 g; n = 573) and a gestational age cohort (gestational age, 23-30 completed weeks; n = 466). Variation in growth status by gestational age was much more uniform in the 23- to 30-week cohort. Thus, although mean birth weight was similar in the 500- to 1,500-g and 23- to 30-week cohorts (1,055 vs. 1,064 g), the 500- to 1,500-g cohort was more mature (mean gestational age, 28.8 vs. 27.8 weeks; upper range, 39.7 vs. 30.9 weeks) and had twice the rate of intrauterine growth retardation (25.7 vs. 11.5%). These differences in maturity and growth resulted in a misleading protective effect of intrauterine growth retardation against in-hospital death in the 500- to 1,500-g cohort (crude odds ratio = 0.55 (95% confidence interval 0.36-0.83] and a greater discrepancy in maturity between cesarean- and vaginally delivered infants (3.1 vs. 1.5 weeks) in the 500- to 1,500-g vs. 23- to 30-week cohorts. These differences arise from inextricable confounding of growth status and maturity in the 500- to 1,500-g cohort, the most mature infants also being the most growth retarded. The removal of well-grown infants with birth weights of greater than 1,500 g from the VLBW cohort leads to a progressively distorted spectrum of growth with advancing gestational age and an artifactual blunting of the beneficial effects of increasing maturity. The authors suggest that whenever fetal growth is an important exposure, outcome, or confounding variable, epidemiologic studies of extremely small or immature newborns should be based on gestational age rather than the VLBW criterion.

Bias

Risks and benefits of paracetamol antipyresis in young children with fever of presumed viral origin.

To examine whether antipyretic therapy in young children is associated with potential risks (interference with enhanced host defences at febrile temperatures) or benefits (improved comfort and behaviour), a randomised, double-blind, placebo-controlled trial of paracetamol was conducted among 225 children 6 months to 6 years of age who presented with acute (less than or equal to 4 days) fever (greater than or equal to 38 degrees C per rectum) without evident bacterial focus of infection. Parents were asked to give paracetamol liquid 10-15 mg/kg or placebo every 4 h as needed for fever and to avoid bathing, sponging, or other pharmacological agents. Parents kept temperature and symptom diaries and recorded changes in child comfort and behaviour according to a pretested, 5-category Likert-type questionnaire 1-2 h after every dose. There were no significant differences between treated and placebo groups in mean duration of subsequent fever (34.7 vs 36.1 h) or other symptoms (72.9 vs 71.7 h). Paracetamol-treated children were more likely to be rated by their parents as having at least a 1-category improvement in activity (38 vs 11%; p = 0.005) and alertness (33 vs 12%; p = 0.036) but no significant differences were noted in mood, comfort, appetite, or fluid intake. That overall improvement in behaviour and comfort with paracetamol was not impressive is underscored by the inaccuracy of parents' "guess" at the end of the trial as to which agent their child had received-45% correct guesses for paracetamol and 52% for placebo. The data suggest that the clinically relevant hazards and benefits of paracetamol antipyresis have been exaggerated.

Acetaminophen

Postterm infants: too big or too small?

Concern over the postterm pregnancy has shifted from that of the difficult delivery of an excessively large fetus to the current concern with death in utero of an undernourished, small-for-date fetus. Studies of postterm pregnancy before the availability of ultrasonography may have included a large proportion of erroneous menstrual dates. The present study of 7000 infants was undertaken to reassess fetal growth in postterm pregnancies in which the expected date of confinement from last normal menstrual period dating was confirmed (+/- 7 days) by early ultrasonography. Results show a gradual shift toward higher birth weight and greater crown-heel length and head circumference between 273 and 300 days of gestational age. No evidence of postterm weight loss or lower weight for length could be demonstrated. Concern in postterm pregnancy should be for fetal macrosomia, not for intrauterine growth retardation.

Birth Weight

An algorithm for the operational assessment of adverse drug reactions. III. Results of tests among clinicians.

To determine how practicing clinicians use a recently developed algorithm for the diagnostic assessment of suspected adverse drug reactions (ADRs), eight clinicians--four board-certified, practicing physicians and four interns--rated the likelihood of 30 suspected ADRs. Each physician reviewed the case summaries, first using implicit clinical judgment and two months later by means of the ADR algorithm. The algorithm significantly improved the reproducibility of the senior clinicians' assessments as compared with their implicit assessments; however, the improvement in the interns' assessments with the algorithm was not significant. The validity of the physicians' assessments, which was measured by comparing their ratings with a consensus rating of the three algorithm developers, was also significantly improved by the use of the algorithm. When used by practicing clinicians, the algorithm improves the reproducibility and validity of their assessments of ADRs and should provide a more precise diagnostic approach to these complex clinical phenomena.

Child

An algorithm for the operational assessment of adverse drug reactions. I. Background, description, and instructions for use.

Despite widespread clinical and epidemiologic attention to adverse drug reactions (ADRs), their clinical identification has been a nonreproducible act of unspecified subjective judgment; adequate operational criteria have not been available for diagnostic decisions about the cause of an observed untoward clinical manifestation. To improve scientific precision in the diagnosis of ADRs, we have developed an algorithm that provides detailed operational criteria for ranking the probability of causation when ADR is suspected between a drug and a clinical manifestation. The algorithm provides a scoring system for six axes of decision strategy: previous general experience with the drug, alternative etiologic candidates, timing of events, drug levels and evidence of overdose, dechallenge, and rechallenge. The sum of the scores is ordinally partitioned to rate the candidate ADR as definite, probable, possible, or unlikely.

Decision Making

An algorithm for the operational assessment of adverse drug reactions. II. Demonstration of reproducibility and validity.

The reproducibility and validity of an algorithm for diagnosis of adverse drug reactions (ADRs) were tested in a clinical spectrum of 30 suspect cases. Using a questionnaire derived from the algorithm the three algorithm developers (nonexperts) agreed on the probability of ADR in 67% of cases, with pair-wise agreement varying from 73% to 87%. The pair-wise agreement of two clinical pharmacologic experts rose from 47% without the algorithm to 63% with the algorithm, with Kw, a chance-corrected index of weighted agreement, increasing from 0.26 to 0.57. The algorithmic assessments of the three nonexperts agreed with expert consensus in 80% to 83% of cases. The ADR algorithm appears to provide a reproducible and valid method of evaluating the likelihood of ADRs in individual patients. Its use can help improve the diagnostic and epidemiologic approach to these important, complex clinical phenomena.

Adult

Accuracy of cord blood screening for sickle hemoglobinopathies. Three- to five-year follow-up.

The strategic advantages of neonatal diagnosis of sickle hemoglobinopathies depend on an accurate cord blood screening procedure. One hundred thirty-eight black children in whom a range of normal and abnormal hemoglobin genotypes was identified by agar gel and cellulose acetate hemoglobin electrophoresis at birth were retested by cellulose acetate three to five years later. The original cord blood diagnoses were verified in all 138, including all 26 with major sickle syndromes (SS, S-beta thalassemia, and SC). Cord blood hemoglobin electrophoresis using these techniques permits accurate neonatal diagnosis of major and minor sickle hemoglobinopathies.

Anemia, Sickle Cell

Adolescent secondary amenorrhea: association with hypothalamic hypothyroidism.

In adolescent girls, secondary amenorrhea can result from a variety of physiologic and psychologic disturbances. Previous reports associating amenorrhea and primary hypothyroidism have not distinguished between the alternative etiologic roles of thyroxine deficiency and hyperprolactinemia. We have evaluated two girls with secondary amenorrhea who had clinical and chemical evidence of hypothyroidism. Both had low basal T4 values (0.8 and 3.2 microgram/dl), calculated free T4 (0.1 and 0.7 ng/dl), and T3 (51 and 81 ng/dl). Both had undetectable basal TSH with normal TSH response to TRH. Basal FSH and LH values were normal, as was the response to LHRH. Basal prolactin levels were 6 and 14 ng/ml, respectively, and both girls had growth hormone responses of greater than or equal to 15 ng/ml in response to insulin-induced hypoglycemia. Pituitary-adrenal function and reserve were also normal. In neither patient was there any historical, physical, or laboratory features compatible with anorexia nervosa. After treatment with 1-thyroxine, both girls had a resumption in menses. These two adolescent girls thus appear to have isolated hypothalamic hypothyroidism. The associated secondary amenorrhea demonstrates that thyroid deficiency alone, without hyperprolactinemia, can interfere with normal hypothalamic-pituitary-ovarian function.

Adolescent