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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↗

PubMed1995

Efficacy and safety of lowering dietary intake of fat and cholesterol in children with elevated low-density lipoprotein cholesterol. The Dietary Intervention Study in Children (DISC). The Writing Group for the DISC Collaborative Research Group.

OBJECTIVE: To assess the efficacy and safety of lowering dietary intake of total fat, saturated fat, and cholesterol to decrease low-density lipoprotein cholesterol (LDL-C) levels in children. DESIGN: Six-center randomized controlled clinical trial. PARTICIPANTS: Prepubertal boys (n = 362) and girls (n = 301) aged 8 to 10 years with LDL-C levels greater than or equal to the 80th and less than the 98th percentiles for age and sex were randomized into an intervention group (n = 334) and a usual care group (n = 329). INTERVENTION: Behavioral intervention to promote adherence to a diet providing 28% of energy from total fat, less than 8% from saturated fat, up to 9% from polyunsaturated fat, and less than 75 mg/4200 kJ (1000 kcal) per day of cholesterol (not to exceed 150 mg/d). MAIN OUTCOME MEASURES: The primary efficacy measure was the mean LDL-C level at 3 years. Primary safety measures were mean height and serum ferritin levels at 3 years. Secondary efficacy outcomes were mean LDL-C levels at 1 year and mean total cholesterol levels at 1 and 3 years. Secondary safety outcomes included red blood cell folate values; serum zinc, retinol, and albumin levels; serum high-density lipoprotein cholesterol (HDL-C) values, LDL-C:HDL-C ratio, and total triglyceride levels; sexual maturation; and psychosocial health. RESULTS: At 3 years, dietary total fat, saturated fat, and cholesterol levels decreased significantly in the intervention group compared with the usual care group (all P < .001). Levels of LDL-C decreased in the intervention and usual care groups by 0.40 mmol/L (15.4 mg/dL) and 0.31 mmol/L (11.9 mg/dL), respectively. Adjusting for baseline level and sex and imputting values for missing data, the mean difference between the groups was -0.08 mmol/L (-3.23 mg/dL) (95% confidence interval [CI], -0.15 to -0.01 mmol/L [-5.6 to -0.5 mg/dL]), which was significant (P = .02). There were no significant differences between the groups in adjusted mean height or serum ferritin levels (P > .05) or other safety outcomes. CONCLUSIONS: The dietary intervention achieved modest lowering of LDL-C levels over 3 years while maintaining adequate growth, iron stores, nutritional adequacy, and psychological well-being during the critical growth period of adolescence.

Analysis of Variance↗

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↗

PubMed1991

Mixed model segregation analysis of LDL-C concentration with genotype-covariate interaction.

Mixed model complex segregation analyses have in the past ignored the possibility of genotype-covariate interaction. Only in the nonmixed model with polygenic heritability equal to zero have segregation analyses been performed that allowed for genotype specific regression of the phenotype on covariates. We present an extension of Hasstedt's [1982] mixed model likelihood approximation which does allow for genotype-covariate interaction in the mixed model. Following description of this approximation, we validate the likelihood calculation by a Monte Carlo procedure based on the actual pedigree and missing data structure used in a complex segregation analysis of low density plus very low density lipoprotein cholesterol (LDL-C + VLDL-C) in baboons. The observed averages of the bootstrap parameter estimates adequately recover the generating values, which included parameters specifying genotype-covariate interaction. We then applied both a traditional complex segregation analysis and an analysis with genotype-covariate interaction to test for the presence of a major locus affecting LDL-C levels in baboons. The model including genotype-covariate interaction was significantly different from the model without interactions, and strongly supported the hypothesis that there is a segregating Mendelian locus as opposed to a random environmental factor. This major locus accounts for approximately 46% of the variance in LDL-C levels, as compared to 40% explained by a locus with no genotype-covariate interaction.

Animals↗

PubMed2026

Effects of Dynamic Neck Sensorimotor Biofeedback Training in Individuals With Mechanical Neck Pain: A Pilot Randomized Controlled Trial.

Mechanical neck pain (MNP) is commonly accompanied by pain-related functional limitations, sensorimotor disturbances, and fear of movement, which together may contribute to persistent disability. This preliminary randomized controlled trial study investigated the short-term effects of dynamic neck sensorimotor-based biofeedback training in individuals with MNP. 20 MNP patients from outpatient clinics were assigned to a biofeedback training group or a control group. The training group underwent dynamic biofeedback exercises twice weekly for 2 weeks, whereas the control group performed repeated cervical movements without biofeedback. Outcomes included cervical kinematics as repositioning errors (RPE), movement units (MU), maximal range of motion (ROM), and subjective measures, including pain intensity, Neck Disability Index (NDI), and Fear-Avoidance Beliefs Questionnaire (FABQ). All participants completed post-intervention assessments; adherence in the training group was 100%, with no missing data and no adverse events reported. Within the biofeedback training group, participants receiving biofeedback training demonstrated greater improvements in cervical repositioning accuracy during flexion (51.95%, p = 0.04) and extension (46.67%, p = 0.02), along with reductions in fear-avoidance beliefs related to physical activity and work (p < 0.05); these changes were less apparent in the active control group. Exploratory regression analyses suggested associations between improvements in repositioning accuracy and pain reduction, and between increased cervical range of motion and improvements in fear-avoidance beliefs related to physical activity. These pilot findings suggest that dynamic sensorimotor biofeedback training may improve proprioceptive acuity and fear-avoidance beliefs in individuals with MNP, supporting further evaluation in an adequately powered randomized trial.

Humans↗

PubMed1990

A Markovian model for comparing incidences of side effects.

For clinical trials that entail observations at successive visits for the occurrence of a side effect, this paper considers a likelihood-based method to compare side effect incidence rates. The method, which employs the assumption of a Markov chain of order one for the vectors of binary responses, handles missing data due to premature withdrawals. An actual numerical example and a simulated example illustrate the technique.

Clinical Trials as Topic↗

PubMed1990

The measurement of change of quality of life in clinical trials.

A model is presented for the measurement of change of quality of life in clinical trials with time under the influence of one or more treatments. Quality of life is regarded as a multidimensional latent variable, and is measured through dichotomous item responses on a number of points in time. Change of quality of life is 'explained' with a latent logistic regression model which may include parameters for the time process, the effects of clinical treatments, and interaction parameters. By assuming the absence of patient/time interaction within treatment groups, the parameters of the time process and the treatment effects can be estimated independently of the latent quality of life parameters at the start of the treatment. Consequently, differential mortality, censoring mechanisms, and other mechanisms causing missing data can be ignored.

Breast Neoplasms↗

PubMed1991

A bibliography and comments on the use of statistical models in epidemiology in the 1980s.

This paper reviews developments in statistical modelling in epidemiology in the 1980's, with emphasis on cohort and case-control studies. The central roles of the logistic and proportional hazard models are highlighted, and it is shown how these models lead to a deeper understanding of classical designs and methods of analysis as well as to efficient new designs and analytical procedures. The important area of model misspecification is discussed, including the problems of omitted latent structure, mis-modelling of available measurements, missing data and errors in measurements. Various designs motivated by the logistic model are illustrated numerically, and designs based on the proportional hazards model are discussed, as are papers on sample size determination. There are brief introductions to the literature on other topics, including attributable risk, disease clustering, family studies and genetics, analysis of disease incidence data, infectious disease, longitudinal data, screening and miscellaneous related topics in statistics. An extensive bibliography is indexed according to the outline of the paper.

Data Interpretation, Statistical↗

PubMed1988

Finding motion parameters from spherical motion fields (or the advantages of having eyes in the back of your head).

A theory is developed for determining the motion of an observer given the motion field over a full 360 degree image sphere. The method is based on the fact that for an observer translating without rotation, the projected circular motion field about any equator can be divided into disjoint semicircles of clockwise and counterclockwise flow, and on the observation that the effects of rotation decouple around the three equators defining the three principal axes of rotation. Since the effect of rotation is geometrical, the three rotational parameters can be determined independently by searching, in each case, for a rotational value for which the derotated equatorial motion field can be partitioned into 180 degree arcs of clockwise and counterclockwise flow. The direction of translation is also obtained from this analysis. This search is two dimensional in the motion parameters, and can be performed relatively efficiently. Because information is correlated over large distances, the method can be considered a pattern recognition rather than a numerical algorithm. The algorithm is shown to be robust and relatively insensitive to noise and to missing data. Both theoretical and empirical studies of the error sensitivity are presented. The theoretical analysis shows that for white noise of bounded magnitude M, the expected errors is at worst linearly proportional to M. Empirical tests demonstrate negligible error for perturbations of up to 20% in the input, and errors of less than 20% for perturbations of up to 200%.

Humans↗

PubMed1989

[General insecurity, "false" and "real" security: arguments for the routine study of hospital patients for anti-HIV].

HIV infection has become an important risk for medical personal. Use of sufficient preventive measures with all patients and patient materials is time consuming, expensive and impracticable. In the present epidemiological situation anti-HIV testing of all hospital patients will give correct information on the presence or absence of HIV infection for 999 of 1000 patients. In addition to the increased safety of medical personal, testing will have several other advantages, some for the HIV infected persons: (1) In patients with HIV-related diseases time consuming delays in diagnosing the disease can be avoided. An earlier start of therapy will improve prognosis. (2) In HIV-infected persons a therapy can be chosen which exerts the least stress to the immune system. This may delay manifestation or progression of HIV-related diseases. (3) By medical surveillance of HIV-infected persons prophylaxis and immediate therapy of opportunistic infections is possible, which may prolong survival time. (4) Counselling of persons previously unaware of their HIV infection will slow down spread of HIV in the population. (5) Missing data on prevalence and incidence of HIV infection in different geographical areas will be available. Apart from the considerable cost reduction by reducing the use of extensive preventive measures to less than 10% of patients, routine screening of all patients is already economic if testing of 10,000 patients will prevent one single new infection by counselling of people with previously unknown HIV infection.

AIDS Serodiagnosis↗