Biomedical subjects

A Ciampi

Publications and source records attributed to A Ciampi.

At least 19 recordsLinked to original sources

PubMed1997

Pilot study and protocol of the Canadian Trial of Atrial Fibrillation (CTAF).

Antiarrhythmic drug prophylaxis in patients with atrial fibrillation (AF) is associated with a high incidence of arrhythmic recurrence. Uncontrolled studies have suggested that low-dose amiodarone may be superior in terms of efficacy to other antiarrhythmic drugs while having an acceptable side effect profile. The Canadian Trial of Atrial Fibrillation (CTAF) is a 25-center study sponsored by the Medical Research Council of Canada to determine the best treatment strategy to maintain sinus rhythm in patients with persistent or paroxysmal AF. Recruitment began in November 1996 and will continue for 1.5 years. Patients are randomized to receive either low-dose amiodarone or conventional antiarrhythmic drug therapy. Patients assigned to the amiodarone group will receive an oral loading regimen of 10 mg/kg/day during a minimum 14-day period. Patients assigned to conventional antiarrhythmic therapy will receive 1 of 2 agents commonly used in AF prophylaxis: sotalol or propafenone. Drug selection and loading, and electrical cardioversion, if necessary, will be performed within 21 days of randomization. The long-term maintenance dose of amiodarone is 200 mg/day. We have planned a minimum follow-up period of 1 year. The primary end point is the time to the first relapse of AF. Data will be analyzed on an intention-to-treat basis. Secondary outcomes are medication toxicity, mortality, major clinical events, costs of each approach, and quality of life. For the purpose of sample size calculations, it is anticipated that recurrence of AF at 1 year will occur in 50% of patients on conventional treatment compared with 35% in those receiving amiodarone. In order to have an 80% power and a 2-tailed type I error of 0.05, assuming a 15% loss to follow-up rate, a total sample size of 400 patients will be required. A pilot study done at the Montreal Heart Institute has shown that the research protocol is feasible.

Amiodarone↗

PubMed1997

Additive beneficial effects of beta-blockers to angiotensin-converting enzyme inhibitors in the Survival and Ventricular Enlargement (SAVE) Study. SAVE Investigators.

OBJECTIVES: This study assessed whether treatment with a beta-adrenergic blocking agent in addition to the use of the angiotensin-converting enzyme (ACE) inhibitor captopril decreases cardiovascular mortality and morbidity in patients with asymptomatic left ventricular dysfunction after myocardial infarction (MI) and whether the presence of neurohumoral activation at the time of hospital discharge predicts the effects of beta-blocker treatment in these patients. BACKGROUND: Both beta-blockers and ACE inhibitors have been shown to have beneficial effects in patients with left ventricular dysfunction but no overt heart failure after MI. These patients often have persistent neurohumoral activation at the time of hospital discharge, and one would expect that patients with activation of the sympathetic nervous system derive the most benefit from treatment with beta-blockers. However, beta-blockers are underutilized in this high risk group of patients, and it is unknown whether their beneficial effects are additive to those of ACE inhibitors. METHODS: We performed a retrospective analysis of data from the Survival and Ventricular Enlargement (SAVE) study and its neurohumoral substudy. The relations between beta-blocker use at the time of randomization and neurohumoral activation and the subsequent development of cardiovascular events were analyzed by use of Cox proportional hazards models controlling for covariates. RESULTS: After adjustment for baseline imbalances, beta-blocker use was associated with a significant reduction in risk of cardiovascular death (30%, 95% confidence interval [CI] 12% to 44%) and development of heart failure (21%, 95% CI 3% to 36%), but the reduction in recurrent MI (11%, 95% CI 13% to 31%) was not significant. These reductions were independent of the use of captopril. Beta-blockers were not found to have a greater effect in patients with neurohumoral activation at the time of hospital discharge. CONCLUSIONS: The beneficial effects of beta-blocker use at the time of hospital discharge in patients with asymptomatic left ventricular dysfunction after MI appear to be additive to those of captopril and other interventions known to improve prognosis. Neurohumoral activation at the time of hospital discharge fails to identify those patients who will derive the greatest benefit from treatment with beta-blockers.

Adrenergic beta-Antagonists↗

PubMed1997

Role of interactions between psychological and clinical factors in determining 6-month mortality among patients with acute myocardial infarction. Application of recursive partitioning techniques to the GISSI-2 database. Gruppo Italiano per lo Studio della Sopravvivenza nell' Infarto Miocardico.

BACKGROUND: Clinical and epidemiological studies support the hypothesis that ischaemic cardiovascular diseases are consistently associated with psychological, social and behavioural factors. Nevertheless, the joint effect of clinical characteristics and psychological variables in determining the prognosis of acute myocardial infarction survivors has been seldom investigated. METHODS AND RESULTS: In the framework of the GISSI-2 trial, the impact of psychological factors on 6-month mortality and their interaction with clinical features was included as an ad hoc research project. Overall, 2449 patients were evaluated, 63 of whom died during the study period. All patients undertook a self-administered questionnaire (Cognitive Behavioural Assessment Hospital Form), investigating 16 psychological dimensions relative to three areas (state variables, vital exhaustion, trait variables). The impact of psychological variables on prognosis and their interaction with clinical variables were investigated by using a tree-growing technique (RECursive Partitioning and AMalgamation-RECPAM) applied to survival analysis. This statistical method allowed the identification of three separate classes, characterized by different prognoses: Class I (presence of vital exhaustion), Class II (concomitance of no vital exhaustion, depression and low levels of anxiety) and Class III (all other patients). After adjusting for the clinical variables, Class I was associated with an intermediate prognosis (hazard ratio [HR] = 2.2; 95% confidence intervals [CI], 1.2-4.0) and Class II to the worst (HR = 3.2; 95% CI = 1.6-6.2), as compared to Class III. High levels of neuroticism and extroversion were associated with a better prognosis. When clinical and psychological variables were simultaneously investigated by RECPAM, Type A behaviour was shown to be an important risk predictor among patients with better clinical conditions, i.e. those eligible for exercise test (HR = 2.6, 95% CI = 1.2-5.5). Finally, a striking difference in the impact of the most predictive clinical variables (exercise test ineligibility, late and early ventricular failure) was found among patients with and without vital exhaustion. CONCLUSIONS: This study shows that acute myocardial infarction survivors are heterogeneous with respect to 6-month mortality according to their psychological profile. More important, the impact of these variables appears comparable to that of very well known clinical risk predictors. The availability of a large study population, together with the use of innovative statistical techniques, allowed us to identify subgroups of patients for whom the joint action of clinical and psychological characteristics has been clearly documented. This suggests the need for incorporating psychological evaluation in the care of acute myocardial infarction patients.

Cohort Studies↗

PubMed1995

Tree-structured prediction for censored survival data and the Cox model.

Prediction trees for the analysis of survival data are discussed. It is shown that trees are useful not only in summarizing the prognostic information contained in a set of covariates (prognostic classification), but also in detecting and displaying treatment-covariates interactions (subgroup analysis). The RECPAM approach to tree-growing is outlined; prognostic classification and subgroup analysis are then formulated within the RECPAM framework and on the basis of the Cox proportional hazards models with a priori strata. Two examples of data analysis are presented. The issue of cross-validation is discussed in relation to computationally cheaper model selection criteria.

Algorithms↗

PubMed1994

Evidence for different clinical subtypes of type 1 diabetes mellitus: a prospective study.

The purpose of this study was to determine whether the sex, age, severity of clinical presentation, presence of ICAs, IAs, and HLA-DR and DQ types could predict, in a cohort of newly-diagnosed diabetic children: (1) the duration of beta-cell function as measured by C-peptide response to a Sustacal meal; and (2) determine if those predictors could identify disease subtypes. A cohort of 170 consecutive patients was followed for 60 months after diagnosis. We found that age (0.0029), sex (0.0136), ICA (0.0001), presence of DKA (0.0070) and C-peptide peak at diagnosis (0.0000) significantly predicted the duration of residual beta-cell function over time. Furthermore, C-peptide secretion at diagnosis, presence of ICA, age and sex allowed the identification of three different prognostic groups with varying acceleration of beta-cell loss.

Adolescent↗

PubMed1994

Parents' versus physicians' values for clinical outcomes in young febrile children.

OBJECTIVE: To compare how parents and physicians value potential clinical outcomes in young children who have a fever but no focus of bacterial infection. METHODS: Cross-sectional study of 100 parents of well children aged 3 to 24 months, 61 parents of febrile children aged 3 to 24 months, and 56 attending staff physicians working in a children's hospital emergency department. A pretested visual analog scale was used to assess values on a 0-to-1 scale (where 0 is the value of the worst possible outcome, and 1 is the value for the best) for 22 scenarios, grouped in three categories according to severity. Based on the three or four common attributes comprising the scenarios in a given group, each respondent's value function was estimated statistically based on multiattribute utility theory. RESULTS: For outcomes in group 1 (rapidly resolving viral infection with one or more diagnostic tests), no significant group differences were observed. For outcomes in groups 2 (acute infections without long-term sequelae) and 3 (long-term sequelae of urinary tract infection or bacterial meningitis), parents of well children and parents of febrile children had values that were similar to each other but significantly lower than physicians' values for pneumonia with delayed diagnosis, false-positive diagnosis of urinary tract infection, viral meningitis, and unilateral hearing loss. For bacterial meningitis with or without delay, however, the reverse pattern was observed; physicians' values were lower than parents'. In arriving at their judgment for group 2 and 3 scenarios, parents gave significantly greater weight to attributes involving the pain and discomfort of diagnostic tests and to diagnostic error, whereas physicians gave significantly greater weight to attributes involving both short- and long-term morbidity and long-term worry and inconvenience. Parents were significantly more likely to be risk-seeking in the way they weighted the attributes comprising group 2 and 3 scenarios than physicians, ie, they were more willing to risk rare but severe morbidity to avoid the short-term adverse effects of testing. CONCLUSIONS: Parents and physicians show fundamental value differences concerning diagnostic testing, diagnostic error, and short- and long-term morbidity; these differences have important implications for diagnostic decision making in the young febrile child.

Attitude of Health Personnel↗

PubMed1993

Different rates of conversion to IDDM in siblings of type 1 diabetic children: the Montreal family study.

This study was undertaken to analyze the risk of developing insulin-dependent diabetes (IDDM) in siblings of type 1 diabetic children. Islet-cell antibodies (ICA) were tested in 568 subjects, siblings of type 1 diabetic children. The subjects were followed prospectively for the conversion to clinical diagnosis of IDDM. As a result siblings who were islet cell antibody (ICA)+ positive at the time of diagnosis of the diabetic sibling (index case) had a significantly higher risk of developing IDDM than those who were ICA-. However, of the 19 siblings who developed IDDM, only 10 were ICA+ at the time of the first test but, 17 became ICA+ before diagnosis of IDDM. The interval between a positive test and the clinical diagnosis of IDDM varied between subjects (6-44 months, mean = 18.4 +/- 4.2 S.E. months) but it was less than 1 year in one subject. In addition to the higher risk of developing IDDM when ICA was positive, male sex and younger age of the subjects as well as young age of the index case and multiplex pedigrees were significant predictors of conversion to IDDM. The Cox's regression tree constructed using RECPAM identified three groups of varying rates of conversion to IDDM: (1) a group with the slowest progression characterized by ICA- and age of index case > 5 years or female sex (relative hazard = 1); (2) an intermediate progression group consisting of subjects who are ICA- and have both < 5 years of age and male sex (relative hazard = 8.78); (3) a group with the fastest progression consisting of subjects who are ICA+ (relative hazard = 31.45). From these results our data suggest that in addition to ICA, clinical markers such as age, sex and multiple pedigrees are also significant predictors of the rate of conversion to IDDM. Furthermore, screening for ICA in family intervention studies will have to be done frequently, perhaps yearly, and will have to be continued into adult life, particularly in ICA- subjects in order to identify the 85-90% of subjects who become ICA+ at the clinical diagnosis of IDDM.

Adolescent↗

PubMed1993

Role of the complete blood count in detecting occult focal bacterial infection in the young febrile child.

Previous studies of the value of the complete blood count (CBC) in distinguishing viral from bacterial infection in young febrile children have failed to exclude children with clinically evident bacterial infection and thus have inflated the positive predictive value of the test for occult focal infection. We prospectively studied 2492 children 3-24 months of age who presented to a children's hospital emergency department between March 1989 and August 1990 with fever (> or = 38.0 degrees C) of acute (< or = 4 days) onset but no evident bacterial focus of infection, 433 (17.4%) of whom received a CBC. We also carried out an 8-year retrospective analysis to estimate prior, or pre-test, probabilities (prevalences) and examine CBC results for rare occult bacterial infections (meningitis, osteomyelitis, and septic arthritis). Estimated prior probabilities for the four most common categories of infection that can be diagnosed at the initial visit were: non-pneumonitic viral infection, 88.6% in boys and 86.0% in girls; pneumonia, 8.5% in both sexes; urinary tract infection (UTI), 3.0% in boys and 5.5% in girls; and bacterial meningitis, 0.0066% in both sexes. The likelihood (sensitivity) of a total white blood cell (WBC) count > or = 15,000/mm3 was 25.5, 64.5, 62.5, and 50.0% for viral infection, pneumonia, UTI, and meningitis, respectively. Among children with a high total white blood cell count, neither a total polymorphonuclear count > or = 10,000/mm3 nor a band count > or = 500/mm3 was associated with significantly elevated likelihoods for occult pneumonia or UTI, a finding confirmed by multiple logistic regression analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

PubMed1993

The longterm prognosis of lupus nephritis: the impact of disease activity.

An inception cohort of 87 patients with lupus nephritis was evaluated using a classification tree regression technique. Four relevant outcomes were studied: (1) renal insufficiency (serum creatinine > 5.0 mg/dl); (2) renal failure; (3) death due to renal involvement; and (4) any death due to systemic lupus erythematosus. All 4 outcomes could be predicted by one or more renal severity measures (serum creatinine, 24-h urinary protein excretion, nephrotic syndrome, or duration of prior renal disease), and among those with nonsevere renal disease, with a single disease activity measure (the National Institutes of Health or le Riche index). In general 3 prognostic groups (high, intermediate and low risk) could be identified for each outcome. Our results demonstrate the value of regression tree techniques in studies of prognosis and are compatible with a hypothesis of the interaction of disease activity with organ damage in lupus nephritis.

Adult↗

PubMed1992

NHPPREG: a computer program for the analysis of nonhomogeneous Poisson process data with covariates.

A program written in C is described which finds maximum likelihood estimates of regression coefficients and other relevant parameters for a point process with covariates. The data are assumed to come from a Poisson point process and may be modelled, at the user's choice, either totally parametrically or semi-parametrically. Furthermore, extra Poisson variation may be introduced, in both the parametric and semi-parametric approach, by the device of random effects. The work closely follows the theory developed by Lawless (1987).

Humans↗

PubMed1991

RECPAM: a computer program for recursive partition and amalgamation for survival data and other situations frequently occurring in biostatistics. III. Classification according to a multivariate construct. Application to data on Haemophilus influenzae type b meningitis.

The methodology of RECursive Partition and AMalgamation (RECPAM) previously presented in Parts I and II (A. Ciampi et al., Computer. Methods Progr. Biomed. 26 (1988) 239-256 and 30 (1989) 283-296) pursues its development with an application to predict long-term effects of a disease given a set of clinical information measured at the time of illness. This paper illustrates how RECPAM deals with a situation typical in Medical Informatics applied to data on Haemophilus influenzae type b meningitis.

Adolescent↗

PubMed1991

The risk of developing disease for siblings of patients with insulin dependent diabetes mellitus.

We analyzed the risk of developing insulin-dependent diabetes mellitus (IDDM) in 411 siblings of patients with IDDM. We found that siblings who had a positive test for antibodies against islet cells (ICA) at the time of diagnosis of the index case had a higher risk of developing IDDM than did those who had negative tests. However, of the ten siblings who developed IDDM, only four were positive at the initial testing. The period of time elapsing from a negative test at screening to a positive test at diagnosis varied but was less than one year in one child. Two of the ten siblings who developed IDDM had negative tests both at screening and at diagnosis. Amongst siblings who were negative at the initial screening, those in whom the index case was diagnosed at a young age had a higher risk of developing IDDM than did those in whom the index case was diagnosed at an older age. The age of the sibling at the time of screening, the sex of the sibling, and a positive family history (one which includes in addition to the index case one or more first-degree relatives with IDDM) did not confer increased risk. Our data suggest that screening for ICA will have to be done often and will have to be continued into adult life in order to identify the 70-80% of diabetics who will be positive at some time in the evolution of their disease.

Adolescent↗

PubMed1990

The sequelae of Haemophilus influenzae meningitis in school-age children.

BACKGROUND: Previous data on the consequences of Haemophilus influenzae type b meningitis for school-age children have been inconsistent, and much of the information on risk factors has been inconclusive. The present study was designed to evaluate the sequelae of this disease with a protocol for the comprehensive assessment of neuropsychological function. METHODS: Ninety-seven school-age children (mean age, 9.6 years), each of whom had a school-age sibling, were recruited from a survey of the medical records of 519 children treated for H. influenzae type b meningitis between 1972 and 1984 (at a mean age of 17 months) at the children's hospitals of Toronto, Ottawa, and Montreal. Of the 97 children, 41 had had an acute neurologic complication. Sequelae were assessed by comparing the index children with their nearest siblings on the basis of standardized measures of cognitive, academic, and behavioral status. RESULTS: Only 14 children (14 percent) had persisting neurologic sequelae: sensorineural hearing loss in 11 (unilateral in 6 and bilateral in 5), seizure disorder in 2, and hemiplegia and mental retardation in 1. Although the total sample of index children scored slightly below the siblings in reading ability, the 56 children without acute-phase neurologic complications (58 percent) were indistinguishable from their siblings on all measures. The differences between the groups were small even for the 41 pairs in which the index child had had an acute neurologic complication (mean full-scale IQ, 102 for the index children vs. 109 for the siblings). Sequelae were also associated with lower socioeconomic status and a lower ratio of glucose in cerebrospinal fluid to that in blood at the time of the meningitis. Behavioral problems were more prominent in index boys than index girls and in those who were older at the time of testing, but sex and age were not related to cognitive or academic sequelae. CONCLUSIONS: We find a favorable prognosis for the majority of children who are treated for meningitis caused by H. influenzae type b.

Adolescent↗

PubMed1990

RECPAM analysis of prognostic factors in patients with stage III breast cancer.

A retrospective chart review was conducted of women with stage III breast cancer seen at the Princess Margaret Hospital between January 1977 and December 1980. Three hundred and sixty-nine patients were available for analysis. These cases were evaluated to determine the prognostic factors of patients presenting with this stage of the disease using a recursive partitioning technique, RECPAM, and a Cox regression model. A non-mathematical description of RECPAM is presented and the advantages of RECPAM over Cox analysis are discussed. The results identify primary tumour size, axillary node involvement, internal mammary node involvement, and estrogen receptor status as the most important prognostic variables. RECPAM identified 3 prognostic groups and simultaneously provided rules based on the prognostic variables to assign patients to poor, intermediate, or good prognosis categories. Patients with estrogen receptor negative tumours, or those with axillary node involvement, primary tumours greater than 5 cm, and serum alkaline phosphatase greater than 60 IU/L, or those with internal mammary node involvement, no skin changes, and serum alkaline phosphatase greater than 60 IU/L, define a group with a poor prognosis. Patients with estrogen receptor positive tumours, no axillary node involvements, and primary tumours greater than 5 cm, or estrogen receptor positive tumours, axillary node involvement, primary tumours greater than 5 cm, but serum alkaline phosphatase less than or equal to 60 U/L, have an intermediate prognosis. The good prognosis group consists of those patients with estrogen receptor positive tumours who have either skin changes or primary tumours less than or equal to 5 cm. The effect of loco-regional and systemic therapy was assessed and there was no association between treatment assignment and prognostic group. On the basis of this RECPAM analysis, we have defined important prognostic variables to be used in the design of clinical trials, and three major patient subgroups which can be used in routine oncologic practice as a guide to patient management.

Biomarkers, Tumor↗

PubMed1990

Cluster analysis of an insulin-dependent diabetic cohort towards the definition of clinical subtypes.

Clinical and biochemical data on 111 consecutive insulin-dependent diabetic children enrolled in a longitudinal prospective study were analyzed to determine if more than one clinical expression of Type I diabetes exists. Use of multivariate statistical methods, including Correspondence Analysis, kappa-means clustering and RECPAM (RECursive Partition and AMalgamation), show that there are two well differentiated clinical expressions of IDDM each characterized by a cluster. One is characterized by later age, less severe onset, longer symptom duration, less beta-cell disappearance after 12 months, more females; the other by earlier age, more sudden and severe onset, DR 3/4, earlier disappearance of beta-cell function and more males. RECPAM analysis provides further insight into the structure of the two clusters. An other RECPAM tree identifies low, medium and high risk groups of disappearance of beta-cell function at 12 months after diagnosis.

Adolescent↗

PubMed1990

Parents' vs physicians' utilities (values) for clinical outcomes in potentially bacteremic children.

Our previous analyses of decision strategies in children 3-24 months with acute-onset fever greater than or equal to 39 degrees C and no evident bacterial focus of infection indicated that the risks of routine blood cultures (the unnecessary hospitalization and treatment of children who clear their bacteremia spontaneously) outweigh its benefits (the prevention of a few cases with major infectious sequelae). Because those analyses were based on parents' values for beneficial and adverse clinical outcomes, we wished to examine whether those values differed in physicians and, if so, whether the differences were sufficient to change the results of the decision analysis. Using a pre-tested linear analog utility (value) scale, we evaluated eight potential clinical outcomes in potentially bacteremic children by surveying 121 parents of healthy 3-24-month-old children attending a private pediatric group practice and 57 attending physicians of a tertiary-care children's hospital emergency room. Utilities were based on a 0-1 normalization, where 0 is the utility of the worst outcome (meningitis or other major bacterial infection, plus venipuncture), and 1 the utility of the best outcome (complete recovery without venipuncture or hospitalization), and were analyzed using a recently developed statistical model of utility. The majority of parents and physicians combined the imputed components of the outcomes (disease, pain of venipuncture, and stress of hospitalization) in a nonlinear fashion. Parents assigned substantially lower utility (i.e. greater disutility) to venipuncture, minor infection, and hospitalization than did physicians, and these utilities were even lower in parents with other children at home.(ABSTRACT TRUNCATED AT 250 WORDS)

Attitude of Health Personnel↗

PubMed1990

X-linked hypophosphatemia: the mutant gene is expressed in teeth as well as in kidney.

Mutation at a locus (HPDR) on the X chromosome (McKusick 30780 [HPDR1]; 30781 [HPDR2]) causes impaired renal phosphate transport, hypophosphatemia, and an associated impairment in the process of mineralization in bone and teeth (X-linked hypophosphatemia [XLH]). We measured the dental pulp profile area (PRATIO [= pulp area/tooth area]) and serum phosphorus (Pi) values in uniformly treated XLH patients (six males, 81 teeth, 1,457 Pi values; 11 females, 129 teeth, 1,439 Pi values). Serum Pi values, reflecting the metabolic environment of tooth development, were obtained by repeated measurement between 1 mo and 26 years of age during treatment. PRATIO values calculated from standardized Rinn radiographs were used as outcome measurements of tooth development in XLH patients and in age-matched controls (12 males, 100 teeth; 27 females, 275 teeth). Age-dependent serum Pi values were not different in the treated XLH males and females. In teeth forming primary dentin there was no gene dosage effect on PRATIO values apparent in subjects below 15 years of age. However, in teeth forming secondary dentin a gene dosage was found in the subjects aged 15 to 25 years: XLH male teeth (n = 65) mean +/- SD = 0.163 +/- 0.046; XLH female teeth (n = 75) mean +/- SD = 0.137 +/- 0.039; control teeth (n = 209) mean +/- SD = 0.116 +/- 0.023; (higher PRATIO values mean less development or mineralization of secondary dentin); differences in these PRATIO values (males vs. female and XLH vs. control) were significant by mixed-model analysis of variance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1989

GENCOV: a Fortran program that generates randomly censored survival data with covariates.

We present a Fortran program for simulating censored survival data with covariates under the assumption of random censoring. The program generates times distributed according to the uniform distribution, the generalized Gamma distribution, the log-normal distribution and Pettitt's generalized logistic distribution with Box-Cox transformation of the time variable. Covariates can be introduced in the definition of the survival time, resulting in the generalized log-gamma, log-normal and Pettitt's regression models. Thereby the program provides the means for generating censored survival data according to parametric versions of three common regression models for censored survival data: the Accelerated Failure Time, the Proportional Hazards and the Proportional Odds models.

Computer Simulation↗