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PubMed1987

Differential diagnosis of jaundice: applicability of the Copenhagen Pocket Chart proved in Stockholm patients.

This paper shows that an algorithm for differential diagnosis of jaundice developed in Denmark has been successfully transferred for use in a Swedish hospital. The algorithm, which is based on data from nearly 1000 patients, utilises 21 items of information from the medical history, physical examination and blood chemistry. The algorithm recognises four diagnostic groups: benign obstructive jaundice, malignant obstructive jaundice, acute non-obstructive jaundice, and chronic non-obstructive jaundice. To each item of information, a score is attached reflecting its weight of evidence. Summing the scores for the symptoms and signs that are present leads to a probabilistic statement about the diagnosis. Because of missing data in the Swedish patient material, three of the items were excluded from the original algorithm. Corrections were made for differences in the distribution of diseases. In reclassification of 985 Danish patients the modified algorithm's "best bid", i.e. the diagnosis given the highest probability, was correct in 78% of cases. More important, 93% of the cases given a "confident" diagnosis (probability greater than 0.80) were correct. The corresponding figures when the algorithm was applied to Swedish patients were 76% and 93%, respectively. In both series the predicted probabilities were matched by a corresponding proportion of actual diagnostic hits. It is concluded that the algorithm leads to reliable estimates of diagnostic probabilities in jaundice and that the algorithm seems to work well in Sweden also.

Adult↗
PubMed1991

Analyzing laboratory marker changes in AIDS clinical trials.

Repeated measurements of laboratory markers of immunologic or disease status, such as CD4 lymphocyte counts and HIV p24 antigen levels, can be important end points in comparative clinical trials. In this report, we consider comparison of treatment groups with respect to such markers, focusing on a distribution-free approach in which each participant's data are characterized by a single summary statistic. The summary statistics examined are (a) the slope of the least-squares regression of the marker, (b) the average of the last r measurements, and (c) the difference between the averages of the last r and the first s measurements. Under various models of marker time trends, these methods are compared with regard to statistical power. It is found that the slope is usually more efficient than the other two types of summaries. Adaptations for missing data are discussed and illustrated in an analysis of CD4 counts from a recent AIDS clinical trial.

Acquired Immunodeficiency Syndrome↗
PubMed1991

A maximum likelihood method for estimating genome length using genetic linkage data.

The genetic length of a genome, in units of Morgans or centimorgans, is a fundamental characteristic of an organism. We propose a maximum likelihood method for estimating this quantity from counts of recombinants and nonrecombinants between marker locus pairs studied from a backcross linkage experiment, assuming no interference and equal chromosome lengths. This method allows the calculation of the standard deviation of the estimate and a confidence interval containing the estimate. Computer simulations have been performed to evaluate and compare the accuracy of the maximum likelihood method and a previously suggested method-of-moments estimator. Specifically, we have investigated the effects of the number of meioses, the number of marker loci, and variation in the genetic lengths of individual chromosomes on the estimate. The effect of missing data, obtained when the results of two separate linkage studies with a fraction of marker loci in common are pooled, is also investigated. The maximum likelihood estimator, in contrast to the method-of-moments estimator, is relatively insensitive to violation of the assumptions made during analysis and is the method of choice. The various methods are compared by application to partial linkage data from Xiphophorus.

Animals↗
PubMedDate not supplied

BACTID: a microcomputer implementation of a PASCAL program for bacterial identification based on Bayesean probability.

A computer program (BACTID) is described which enables the identification of bacteria based on a priori data and Bayesean probability testing. The program is not limited to a specific format, has a short execution time, can be easily applied to a variety of situations, and can be run on almost any microcomputer system operating under either 8-bit CP/M or 16-bit MS-DOS or PC-DOS. Additionally, BACTID is not limited to one type of computer (hardware independent); is not limited by size of the computer's random access memory (RAM independent); can recognize various database matrices (format independent); is able to compensate for missing data; and allows for various methods of data entry. The efficacy of the program was checked against a commercially available test system and a 99.34% agreement was obtained. Also, the execution time for a 46 x 21 data matrix was as little as 3.5 seconds. These results show that microcomputer identification programs not only are viable alternatives to code-book registers, but also offer flexibility which is not found in commercial systems.

Bacteria↗
PubMed1992

Accounting for the correlation between fellow eyes in regression analysis.

Regression techniques that appropriately use all available eyes have infrequently been applied in the ophthalmologic literature, despite advances both in the development of statistical models and in the availability of computer software to fit these models. We considered the general linear model and polychotomous logistic regression approaches of Rosner and the estimating equation approach of Liang and Zeger, applied to both linear and logistic regression. Methods were illustrated with the use of two real data sets: (1) impairment of visual acuity in patients with retinitis pigmentosa and (2) overall visual field impairment in elderly patients evaluated for glaucoma. We discuss the interpretation of coefficients from these models and the advantages of these approaches compared with alternative approaches, such as treating individuals rather than eyes as the unit of analysis, separate regression analyses of right and left eyes, or utilization of ordinary regression techniques without accounting for the correlation between fellow eyes. Specific advantages include enhanced statistical power, more interpretable regression coefficients, greater precision of estimation, and less sensitivity to missing data for some eyes. We concluded that these models should be used more frequently in ophthalmologic research, and we provide guidelines for choosing between alternative models.

Adolescent↗
PubMed1987

[Prognostic factors in operated non-small cell cancer of the lung. Study from a randomized therapeutic trial].

This article presents the results of a prognostic study of primary resected lung cancer (non-small cell). The data result from a randomised clinical trial of immunotherapy with a non-specific adjuvant; the follow-up was between four to seven years. Thirty-five clinical, biological and anatomo-pathological parameters were gathered at the time of inclusion in the trial. The response criteria used were survival without recurrence and total survival. A multivariate analysis using the Cox's model was carried out for each criterion. At the reference date of the 1st April 1985, 125 relapses and 132 deaths were counted amongst 219 patients; there was only one patient lost to follow-up and only 39 missing data were observed. The negative therapeutic results of the immunotherapy used were confirmed by this new intermediate analysis. The rate of survival without recurrence at 5 years was 43% and the overall survival at five years was 42%. The use of Cox's model to show the prognostic information at the 5% level for survival without recurrence could be summarised by five factors: main staging (the prognostic factor), leucocytosis, the cutaneous reaction to proteus, Karnofsky index and presence of physical signs. For stages I and II the outcome was identical and no factor was predictive at the 5% level. For stage III the cutaneous reaction to proteus and leucocytosis were prognostic. For overall survival, the prognostic information at the 5% level could be summarised by five factors: staging (main prognostic factor), leucocytosis, Karnofsky index, presence of physical signs and lymphocytosis. For stages I and II whose outcome was identical only Karnofsky index and lymphocytosis were predictive at the 5% level.(ABSTRACT TRUNCATED AT 250 WORDS)

Carcinoma, Non-Small-Cell Lung↗
PubMedDate not supplied

Intentionally incomplete longitudinal designs: I. Methodology and comparison of some full span designs.

Longitudinal designs are important in medical research and in many other disciplines. Complete longitudinal studies, in which each subject is evaluated at each measurement occasion, are often very expensive and motivate a search for more efficient designs. Recently developed statistical methods foster the use of intentionally incomplete longitudinal designs that have the potential to be more efficient than complete designs. Mixed models provide appropriate data analysis tools. Fixed effect hypotheses can be tested via a recently developed test statistic, FH. An accurate approximation of the statistic's small sample non-central distribution makes power computations feasible. After reviewing some longitudinal design terminology and mixed model notation, this paper summarizes the computation of FH and approximate power from its non-central distribution. These methods are applied to obtain a large number of intentionally incomplete full-span designs that are more powerful and/or less costly alternatives to a complete design. The source of the greater efficiency of incomplete designs and potential fragility of incomplete designs to randomly missing data are discussed.

Longitudinal Studies↗
PubMed1989

Interpretation of data on dietary intake.

Although this discussion has focused on the interpretation of dietary data, assuming that it is representative of actual and usual intake and that the nutrient analysis based on it involved the use of up-to-date food composition tables, the readers should be sensitive to other potential sources of error or bias in obtaining information on food and/or nutrient intake. These include errors due to irregularity of food consumption, under- or overreporting of intake, errors in reporting either the amount or the description of the food consumed, recording errors on the part of the interviewer or coding errors on the part of the coder, limitations in the tables of food composition due to missing data for certain nutrients in certain foods or to biologic variability in the same foods from different sources or in those marketed under different conditions, imputed values, the unknown composition of formulated foods or foods prepared from home or commercial recipes, differences in bioavailability of nutrients as a function of the diet, or the use of abridged tables of food composition. In spite of the many unresolved issues relating to dietary standards and the interpretation of dietary intake data, we are still able to make a reasonable assessment of dietary adequacy of groups and individuals with our current system, which is viewed as a unique federal resource. It is hoped that the eventual passage of the National Nutrition Monitoring and Related Research Act will provide both the impetus and the resources to permit us to develop a more sophisticated system for assessing both food intake and nutritional status.

Data Interpretation, Statistical↗
PubMed1995

Bivariate logistic regression analysis of childhood psychopathology ratings using multiple informants.

A central issue in studies of risk factors for childhood psychopathology is utilization of the information obtained about the child's mental health status from multiple informants. In this paper, the authors propose a new approach to the analysis of risk factor data when the outcomes are binary ratings (presence/absence of symptoms). This new approach has several attractive features in this setting. The strategy taken is to perform a single analysis using multivariate modeling, in which simultaneous logistic regressions are conducted for the outcomes given by each of several informants. The advantages of this approach include the following: 1) it retains the complete information about case status for each informant; 2) it permits assessment of informant-risk factor interactions as well as "overall" risk factor effects; 3) it provides measures of association between the multiple informants and adjusts for the association between responses in the analysis; and 4) missing data on a subset of respondents can be incorporated in a straightforward way, permitting all subjects with at least one informant to be used in the analysis. To illustrate the methods, the authors present findings on risk factors for measures of "Internalizing" and "Externalizing" behaviors from two surveys using parent and teacher ratings of 6- to 11-year-old children in Connecticut between 1986 and 1989.

Child↗
PubMed1992

Delayed neuronal death and delayed neuronal recovery in the human brain following global ischemia.

The understanding of delayed hippocampal death as a therapeutic window for post-ischemic treatment of the brain has led to numerous investigations focusing upon underlying cellular mechanisms and pharmacological potentials in gerbils and rats. Nevertheless, studies on the occurrence of delayed neuronal death in the human brain have been singular and dealt with only small files of patients. To complement these limited data, in the present study 26 adult patients with a history of a single cardiac arrest were included. Following successful resuscitation, individual survival ranged from less than 1 h to 186 days (mean = 11 days). The severity of the resultant ischemic injury in hippocampus CA1, among Purkinje cells, or in frontal neocortex, respectively, was quantified by direct counting of necrotic neurons. Additionally, hippocampal specimens were immunostained for neuron-specific enolase. The data obtained demonstrate the occurrence of delayed neuronal death in human hippocampus and, in a minor form, in cerebellar Purkinje cells. This is in contrasts to the immediate manifestation of ischemic neuronal necrosis in the neocortex. Unlike previous findings in experimental animals and in humans, the delay of CA1 cell death could be defined as lasting about 7 days following cardiac arrest. Moreover, the immunohistochemical results indicate delayed neuronal recovery in CA1, which in the time course reciprocally corresponds to delayed manifestation of hippocampal neuronal death. Interpretation of the results must consider the lack of information about the exact individual duration of cardiac arrest and resuscitation, as well as missing data concerning pre-ischemic physiological variables.

Adult↗
PubMed1987

A deductive method of haplotype analysis in pedigrees.

Derivation of haplotypes from pedigree data by means of likelihood techniques requires large computational resources and is thus highly limited in terms of the complexity of problems that can be analyzed. The present paper presents 20 rules of logic that are both necessary and sufficient for deriving haplotypes by means of nonstatistical techniques. As a result, automated haplotype analysis that uses these rules is fast and efficient, requiring computer memory that increases only linearly (rather than exponentially) with family size and the number of factors under analysis. Some error analysis is also possible. The rules are completely general with regard to any system of completely linked, discrete genetic markers that are autosomally inherited. There are no limitations on pedigree structure or the amount of missing data, although the existence of incomplete data usually reduces the fraction of haplotypes that can be completely determined.

Genetic Markers↗
PubMed1989

A robust orthogonal algorithm for system identification and time-series analysis.

We describe and illustrate methods for obtaining a parsimonious sinusoidal series representation or model of biological time-series data. The methods are also used to identify nonlinear systems with unknown structure. A key aspect is a rapid search for significant terms to include in the model for the system or the time-series. For example, the methods use fast and robust orthogonal searches for significant frequencies in the time-series, and differ from conventional Fourier series analysis in several important respects. In particular, the frequencies in our resulting sinusoidal series need not be commensurate, nor integral multiples of the fundamental frequency corresponding to the record length. Freed of these restrictions, the methods produce a more economical sinusoidal series representation (than a Fourier series), finding the most significant frequencies first, and automatically determine model order. The methods are also capable of higher resolution than a conventional Fourier series analysis. In addition, the methods can cope with unequally-spaced or missing data, and are applicable to time-series corrupted by noise. Finally, we compare one of our methods with a well-known technique for resolving sinusoidal signals in noise using published data for the test time-series.

Algorithms↗
PubMed1991

Treatment of migraine attacks with sumatriptan.

BACKGROUND: The headache in migraine attacks may be caused by dilatation of certain cranial arteries or arteriovenous anastomoses, by neurogenic dural plasma extravasation, or by both of these mechanisms. Sumatriptan, a novel selective agonist of 5-hydroxytryptamine-like receptors, blocks these phenomena. We investigated its efficacy in migraine. METHODS: We studied 639 patients with migraine attacks in a randomized, double-blind, placebo-controlled, parallel-group clinical trial. We assessed the effect of subcutaneous injections of 6 or 8 mg of sumatriptan or placebo on the severity of headache and associated migrane symptoms 30, 60, and 120 minutes after treatment. Patients who were not free of pain after 60 minutes subsequently received placebo if they had initially received placebo or 8 mg of sumatriptan, and 6 mg of sumatriptan or placebo if they had initially received 6 mg of sumatriptan. RESULTS: After 60 minutes, the severity of headache was decreased in 72 percent (95 percent confidence interval, 68 to 76 percent) of the 422 patients given 6 mg of sumatriptan, 79 percent (95 percent confidence interval, 71 to 87 percent) of the 109 patients given 8 mg of sumatriptan, and 25 percent (95 percent confidence interval, 17 to 33 percent) of the 105 patients given placebo (data on 3 patients could not be evaluated). As compared with the placebo group, 47 percent (95 percent confidence interval, 38 to 57 percent) more patients who had received 6 mg of sumatriptan and 54 percent (95 percent confidence interval, 43 to 65 percent) more patients who had received 8 mg of sumatriptan had a decrease in the severity of headache (P less than 0.001 for both comparisons). After 120 minutes, 86 to 92 percent of the 511 patients treated with sumatriptan (202 assigned to 6 mg plus placebo, 203 to 6 mg plus 6 mg, and 106 to 8 mg plus placebo) had improvement in the severity of headache, as compared with only 37 percent of the 104 patients who received placebo once or twice (P less than 0.001 for all comparisons). Twenty-one patients were excluded from the analysis because of missing data (19) or protocol violations (2). The response rates did not differ significantly among the sumatriptan regimens. Adverse events were minor and transient in all groups. CONCLUSIONS: We conclude that a single 6-mg dose of sumatriptan given subcutaneously is a highly effective, rapid-acting, and well-tolerated treatment for migrane attacks. The administration of a second dose 60 minutes later to patients not responding well to an initial dose affords little additional benefit.

Adolescent↗
PubMed1988

Demographic, clinical, and financial factors relating to the completion rate of screening mammography.

A retrospective analysis of the UCLA Family Health Center Research Data Base was performed to determine the relationship between completion rates of screening mammography and various patient demographic, clinical, and financial factors. Data from a 16-month period, from July 1984 through October 1985, were analyzed. Eight hundred twenty-seven women over 50 years of age were seen in the UCLA Family Health Center at least once during the study period. One hundred thirty-six (16.4%) of these women had screening mammography performed. Health insurance coverage was an important determinant of mammography completion. Patients covered by a health maintenance organization were 2.5 (P less than .05) times more likely to receive screening mammography. Uninsured patients were only 0.5 times as likely to have this procedure performed. The completion rate for screening mammography increased significantly with increasing number of visits during the study period (P less than .001). The age groups analyzed were significantly associated with completion rate. Marital status had a significant relationship to completion rate, but this was due to a lower completion rate in the group of patients whose marital status could not be determined. The employment status could not be evaluated due to the high rate of missing data. Race, smoking status, alcohol consumption, and the sex and training level of the primary provider were not found to be significantly associated with screening mammogram completion rates.

Aged↗
PubMed1982

Teenage pregnancy and parenthood: outcomes for mother and child.

This study reports some general health and related outcomes for all women ages 14, 15, and 16 and their children delivered at our hospital in 1976. These outcomes are contrasted with 100 women ages 20-30 years and their children born the same year. Data were collected by retrospective chart review. For the teenage group, 70% were unmarried, most of the fathers were 4-5 years older than the teenaged mother, most teen mothers were living with their parents, and all had incomes in the poverty range. A comparison of black and white teenaged mothers showed that: (1) 14-15-year-old blacks had proportionally more pregnancies than whites, (2) the first prenatal visit was later for blacks, and (3) children of the white teenagers had more acute illness visits during the 2-yr follow up. When the age of the teenage mother is considered, the 1-min Apgar scores for the children of 14-year olds were lower and the school drop out rate was higher with increasing maternal age. In comparing the teen to the 20-30-year-old group, the only finding was higher complication rate for pregnancy and delivery for the teen group. The physical growth of all children was normal. These results must be interpreted with caution, because of missing data for some variables; however, this data should be of some use in planning future research and intervention programs.

Adolescent↗
PubMed1989

Therapy: state-of-the-art assessment of quality. The National Cancer Institute perspective.

The National Cancer Institute (NCI) has a broad spectrum of responsibilities that range from support of basic laboratory research to the clinical testing of new therapeutics and, finally, the dissemination of results of this research to the practicing physician and the public. The reduction of cancer mortality is largely dependent on the responsibility for widespread application of state-of-the-art cancer treatments. A major cancer control focus of the NCI over the last decade has been the development and implementation of programs designed to improve awareness, access and application of state-of-the-art cancer treatment. In addition to the computerized Physician Data Query system, three targeted programs, the Cooperative Group Outreach Program (CGOP), the Community Hospital Oncology Program (CHOP), and the Community Clinical Oncology Program (CCOP) have all been aimed at establishing mechanisms to facilitate the transfer of new patient care technology; and, thereby, provide the highest quality cancer treatment in the community setting. An evaluation was conducted to determine if patterns and outcomes of cancer care management changed over time, and whether this could be related to the presence of CGOP, CHOP, and CCOP. Measurement of required program implementation was relatively straightforward. However, measurement of resultant changes in "quality of care" and the factors that influence physician performance are complex and controversial. Critical elements in the treatment of breast, colon, rectum, and small cell lung cancer were used as tracers to measure changes in the patterns of care in communities where programs were implemented. Results from this study highlight issues in state-of-the-art assessment of quality, such as the difficulty in defining quality cancer care, relationships between process and outcome indicators, and the problems of documentation and missing data. Assurance of quality cancer care requires the interaction of health care professionals with knowledge of the most up-to-date cancer research results working in a health care delivery system that encourages and rewards application of these results.

Clinical Trials as Topic↗
PubMed2026

Bilateral Conversion Risk in Unilateral Retinoblastoma Using Age and Genetic Testing.

IMPORTANCE: Metachronous bilateral conversion in initially unilateral retinoblastoma is uncommon but clinically consequential, potentially requiring intensified treatment and carrying worse prognosis. Clarifying how age at diagnosis refines genetic-risk stratification could enable safer, more efficient surveillance protocols. OBJECTIVE: To estimate the incidence and timing of metachronous bilateral conversion in unilateral retinoblastoma and assess whether age at diagnosis and RB1 testing are associated with bilateral conversion risk. DESIGN, SETTING AND PARTICIPANTS: This was a retrospective cohort study at a tertiary center in Shanghai, China, including 1108 consecutive children with initially unilateral retinoblastoma diagnosed from July 2010 to October 2024 (after exclusions for short follow-up [n = 139], missing data [n = 53], or synchronous bilateral disease [n = 10]). The median (IQR) follow-up was 43.4 (24.2-67.6) months. EXPOSURES: Age at diagnosis and RB1 genetic status/subtypes assessed by next-generation sequencing and multiplex ligation-dependent probe amplification, including penetrance class (high vs low) and mosaic vs germline categorization. MAIN OUTCOMES AND MEASURES: Time to metachronous bilateral conversion; cumulative incidence functions with death as a competing risk; spatial distribution of fellow-eye tumors. RESULTS: Among 1108 patients (median [IQR] age at diagnosis, 22.2 [12.0-31.4] months; 591 [53.3%] male), 24 (2.2%) developed metachronous bilateral disease. At 24 months, cumulative incidence was 2.2% (95% CI, 1.3-3.1) overall. By genetic status, the 24-month cumulative incidence was 24.8% (95% CI, 13.8-35.9) in RB1 variant-positive vs 1.6% (95% CI, 0.0-3.1) in RB1 variant-negative patients. Among RB1 variant-positive patients, risk clustered among those diagnosed before 9 months, whereas no conversions were observed among those diagnosed at older than 9 months. Four RB1 variant-negative patients who were initially diagnosed at notably late ages (20.9, 42.7, 79.6, and 118 months) subsequently converted; these cases likely represent undetected low-level mosaicism, somatic variants below detection thresholds, or rare genomic events not captured by standard sequencing panels. Fellow-eye tumors did not involve macula and showed a nasal-predominant distribution. CONCLUSIONS AND RELEVANCE: The findings in this study suggest that age at diagnosis may refine genetic risk stratification for metachronous bilateral conversion. RB1 variant-positive patients diagnosed at 9 months or later represent a very low-risk subgroup that may warrant surveillance deescalation, while rare late conversions in RB1 variant-negative patients necessitate continued long-term monitoring.

Humans↗
PubMed1987

Local therapy in stage I clear cell adenocarcinoma of the vagina.

Of the 219 cases of Stage I vaginal clear cell adenocarcinoma reviewed, 176 had conventional therapy and 43 underwent local therapy. The two groups appear to be similar with respect to symptoms, stage, location of the lesion in the vagina, greatest tumor diameter, surface area, depth of invasion, predominant histologic pattern, grade, and number of mitoses; nonetheless, firm conclusions cannot be drawn because of missing data. Actuarial survival rates at 5 and 10 years for the local therapy group (92% and 88%, respectively) were essentially equivalent to those for the conventional therapy group (92% and 90%, respectively), however, the recurrence experience after local therapy was less favorable. Local therapy consisted of vaginectomy in nine cases, local excision alone in 17 cases, and local irradiation (with or without local excision) in 17 cases. The subgroup of patients receiving local irradiation had a recurrence experience as favorable as that of the conventional therapy group and more favorable than that of either the subgroup treated with vaginectomy or local excision alone. The data suggest that when employed, local therapy should include local irradiation.

Adenocarcinoma↗