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Longitudinal analysis of the outcomes of a transitional care program documented success in discharging patients home with remarkable compliance to discharge plans and sustained improvement in mental status and functional independence. Inpatient costs were significantly reduced.
The genetic factors that mediate the pathogenesis of multiple primary cutaneous basal cell carcinomas (BCC) are largely unclear. Thus, some patients suffer many BCC (>30) and/or rapid accrual (number of tumours/year from first presentation) of further lesions. We have studied, in 827 English Caucasians, the influence of polymorphism in carcinogen-metabolizing enzymes on susceptibility to this cancer. Accordingly, we describe, first, a cross-sectional analysis of the influence of GSTM1, GSTT1, CYP2D6 and CYP1A1 genotypes on tumour numbers, and secondly, a longitudinal analysis, in 169 of these cases, of the effect of these genes on tumour accrual. We have confirmed the expected importance of age and number of lesions at presentation, and male gender and skin type as risk factors. Furthermore, the cross-sectional analysis showed CYP1A1 m1m1 (P = 0.004; rate ratio 1.242) and CYP2D6 EM (P < 0.001, rate ratio 1.266) are associated with increased numbers of BCC. The longitudinal study showed, after adjustment for age and tumour number at presentation, that GSTT1 null (P < 0.001, rate ratio 2.677) and CYP2D6 EM (P < 0.001, rate ratio 2.154) were significant determinants of accrual while CYP1A1 Ile/Ile was associated with slower accrual than the Ile/Val and Val/Val genotypes (P = 0.008, rate ratio 0.690). We believe these are the first genetic factors to be associated with tumour accrual. No significant interactions between genotypes were identified, though the combinations GSTM1 null/skin type 1 (P < 0.001, rate ratio 2.702), CYP2D6 EM/male gender (P = 0.049, rate ratio 1.279) and CYP2D6 EM/blue+green eyes (P = 0.046, rate ratio 1.388) influenced tumour numbers. Previous studies indicate the importance of effective repair of UV-damaged DNA in the pathogenesis of multiple BCC; indeed the influence of GSTM1 may result from its ability to utilize 5'-hydroxymethyluracil. However, the finding that CYP2D6 and CYP1A1 influence tumour numbers and accrual indicates detoxification of unknown molecules is important and supports the view that factors other than UV are important in the pathogenesis BCC.
OBJECTIVE: The aim of the current study was to determine levels of circulating endothelial cell adhesion molecules during preeclampsia and to assess their predictive value as diagnostic markers for the early identification of pregnant women at risk of developing preeclampsia. STUDY DESIGN: Plasma samples were obtained from women with preeclampsia; the syndrome of hemolysis, elevated liver enzymes, and low platelets; uncomplicated pregnancy-induced hypertension; and women with normal pregnancy. In addition, longitudinal plasma profiles of pregnant women were randomly collected to determine individual profiles of circulating endothelial cell adhesion molecules. A sandwich enzyme-linked immunosorbent assay technique was used to quantitate concentrations of soluble intercellular adhesion molecule-1 (CD54), vascular cell adhesion molecule-1 (CD106), E-selectin (CD62E), platelet endothelial cell adhesion molecule (CD31), and P-selectin (CD62P). RESULTS: Plasma levels of intercellular adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin, and platelet endothelial cell adhesion molecule-1 were significantly elevated in women with preeclampsia compared with healthy control pregnant women. Longitudinal analysis of soluble plasma intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 levels during pregnancy revealed that these molecules (1) show little variation in healthy pregnant women, (2) do not vary during normal pregnancy, and (3) are significantly elevated in women with preeclampsia and the syndrome of hemolysis, elevated liver enzymes, and low platelets compared with control pregnant women and those with uncomplicated pregnancy-induced hypertension. Analysis of soluble intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 levels in longitudinal profiles of pregnant women identified significantly elevated levels of these molecules in the plasma of preeclampsia-prone women 3 to 15 weeks before the onset of clinical symptoms. CONCLUSION: Elevated soluble intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 measurements during pregnancy can be considered as major risk factors. Elevated levels of these substances in the plasma of pregnant women with preeclampsia support the concept of a primary endothelial cell involvement in the pathogenesis of preeclampsia. Although currently based on a limited database, significantly elevated levels of soluble intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in the plasma of otherwise healthy pregnant women suggest a very high predictive value of these molecules for the earliest identification of women at risk of developing preeclampsia.
A Dutch kindred was studied with low-frequency sensorineural hearing impairment linked to a new locus on chromosome 4p16 (DFNA14). Of the affected individuals, 21 (aged 11-75 years) were examined and the most recent audiogram was used for cross-sectional analysis of hearing threshold in relation to age. Suitable serial audiograms were available for a longitudinal analysis in nine cases: they had been obtained from the age of six years onwards and covered a follow-up period from 14 to 36 years. The presumably congenital (offset) component of SNHI was extrapolated or estimated from average values and offset thresholds were found of about 45 dB at 0.25-1 kHz, 25 dB at 2 kHz and 10 dB at 4-8 kHz. Significant progression in hearing impairment occurred at all frequencies, but could be attributed to presbyacusis. The combination of congenital, stationary low-frequency SNHI and presbyacusis resulted in an up-sloping audiogram in the first five decades of life, which evolved into a flat-type audiogram in the sixth or seventh decade and a down-sloping audiogram at a more advanced age. With few exceptions, vestibular function was intact.
This paper presents an analysis of a longitudinal multi-center clinical trial with missing data. It illustrates the application, the appropriateness, and the limitations of a straightforward ratio estimation procedure for dealing with multivariate situations in which missing data occur at random and with small probability. The parameter estimates are computed via matrix operators such as those used for the generalized least squares analysis of catetorical data. Thus, the estimates may be conveniently analyzed by asymptotic regression methods within the same computer program which computes the estimates, provided that the sample size is sufficiently computer program which computes the estimates, provided that the sample size is sufficiently large.
The aims of this paper were to present data on the pharmacokinetics, clearance, bioavailability, and in vivo absorption of etonogestrel (ENG); to present the results of a longitudinal analysis of the plasma concentration-time curves of ENG; and to present the results of a cross-sectional analysis on the association of body weight with serum ENG concentrations. Implanon had an absorption rate of almost 60 micrograms/day after 3 months, which slowly decreased to 30 micrograms/day at the end of 2 years. The bioavailability over this period of time was constant and close to 100%. The clearance remained around 7.5 L/h. With a bioavailability and clearance that remained constant, it was concluded that accumulation of ENG does not occur. After Implanon insertion, serum concentrations increased within 8 h to concentrations associated with ovulation inhibition. Maximum mean serum concentrations (Cmax) amounted to 813 pg/mL and the time (tmax) to reach Cmax was 4 days. After reaching Cmax, ENG serum concentrations declined to about 196 pg/mL at the end of the first year, followed by a slow decline to 156 pg/mL at the end of the third year. After removal of Implanon, serum ENG concentrations declined to levels less than the detection limit of the assay (20 pg/mL) within 1 week. Lower body weight was associated with higher serum ENG concentrations.
Rat pups exposed to cocaine via maternal intromission throughout gestation and lactation displayed significantly prolonged auditory brainstem response component latencies and interwave intervals. Longitudinal analysis revealed that this effect was most pronounced on the 22nd postnatal day. Increasing the rate of stimulation further impaired neurosensory transmission in the caudal auditory pathway. These results indicate that both axonal and synaptic events may be affected to some degree and the timing (age) of optimum cocaine influence suggests that delayed myelination may be involved. The corresponding retardation in general development of the cocaine exposed pups further implicates maternal, fetal and postnatal utilization of nutritional resources as the basis for this outcome.
Inheritance and expression of mitochondrial DNA (mtDNA) mutations are crucial for the pathogenesis of Leber hereditary optic neuropathy (LHON). We have investigated the segregation and functional consequences of G3460A mtDNA mutation in 27 members of a three-generation family with LHON syndrome. Specific activity of respiratory chain complex I in platelets was reduced in average to 56%, but no direct correlation between the mutation load and its biochemical expression was found. Heteroplasmy in blood, platelets and hair follicles varied from 7% to 100%. Segregation pattern exhibited tissue specificity and influence of different nuclear backgrounds in four branches of the pedigree. Longitudinal analysis revealed a significant (p=0.02) decrease in blood mutation load. Although enzyme assay showed reduction of complex I activity, our results give additional support to the hypothesis that expression of LHON mutation depends on complex nuclear-mitochondrial interaction.
The aim of this prospective study was to assess the impact of intraoral soft-tissue reconstruction on the development of quality of life after ablative surgery for oral cancer. A total of 107 patients were enrolled in the study during the period between 1997 and 1999. Quality of life was assessed by using the quality-of-life core questionnaire and the head and neck module of the European Organization for Research and Treatment of Cancer. The questionnaires were distributed to the patients preoperatively on the day of hospital admission and 3 months, 6 months, and 12 months postoperatively. A total of 53 patients filled in all questionnaires and were available for complete longitudinal analysis. The changes in the scores and the impact of defect size, location, and anatomy, the extent of mandibular resection, and the mode of soft-tissue reconstruction were tested longitudinally for statistical significance by using repeated-measures analysis of variance procedures. Of all parameters tested, the mode of soft-tissue reconstruction had the most profound impact on the development of quality of life after ablative surgery for oral cancer in that it was associated with statistically significant changes in the most domains or items associated with postoperative quality of life. In contrast to local flaps, revascularized soft-tissue repair with forearm flaps was associated with an intermittent deterioration of physical and functional scores but was followed by improvement until the end of the first year, and it even surpassed the preoperative baseline level in oral functional and social domains. In large-volume defects, which required repair by myocutaneous grafts, quality of life was not restored to the same extent, and physical, functional, and social domains remained significantly lower.
BACKGROUND: There are few theoretically derived questionnaires of physical activity determinants among youth, and the existing questionnaires have not been subjected to tests of factorial validity and invariance. The present study employed confirmatory factor analysis (CFA) to test the factorial validity and invariance of questionnaires designed to be unidimensional measures of attitudes, subjective norms, perceived behavioral control, and self-efficacy about physical activity. METHODS: Adolescent girls in eighth grade from two cohorts (N = 955 and 1,797) completed the questionnaires at baseline; participants from cohort 1 (N = 845) also completed the questionnaires in ninth grade (i.e., 1-year follow-up). Factorial validity and invariance were tested using CFA with full-information maximum likelihood estimation in AMOS 4.0. Initially, baseline data from cohort 1 were employed to test the fit and, when necessary, to modify the unidimensional models. The models were cross-validated using a multigroup analysis of factorial invariance on baseline data from cohorts 1 and 2. The models then were subjected to a longitudinal analysis of factorial invariance using baseline and follow-up data from cohort 1. RESULTS: The CFAs supported the fit of unidimensional models to the four questionnaires, and the models were cross-validated, as indicated by evidence of multigroup factorial invariance. The models also possessed evidence of longitudinal factorial invariance. CONCLUSIONS: Evidence was provided for the factorial validity and the invariance of the questionnaires designed to be unidimensional measures of attitudes, subjective norms, perceived behavioral control, and self-efficacy about physical activity among adolescent girls.
Several factors for chronic kidney disease (CKD), including diabetes, hypertension, and obesity, are described consistently in the literature; studies describing modifiable lifestyle factors, including smoking and consumption of alcohol, are sparse, sometimes contradictory. The authors examined the factors associated with CKD in a population-based cohort in Wisconsin, with emphasis on smoking and consumption of alcohol. CKD was defined as an estimated glomerular filtration rate of less than 60 ml/minute per 1.73 m(2) from serum creatinine. The authors performed two analyses: 1) cross-sectional analysis among 4,898 persons with prevalent CKD (n = 324) as the outcome of interest and 2) longitudinal analysis among 3,392 CKD-free persons at baseline, with 5-year incident CKD (n = 114) between 1993 and 1995 as the outcome of interest. Smoking and heavy drinking, defined as consumption of four or more servings of alcohol per day, were associated with CKD, independent of several important confounders. Compared with that among never smokers, the odds ratio of developing CKD was 1.12 (95% confidence interval (CI): 0.63, 2.00) among former smokers and 1.97 (95% CI: 1.15, 3.36) among current smokers. Heavy drinking was associated with CKD, with an odds ratio of 1.99 (95% CI: 0.99, 4.01). Joint exposure to both current smoking and heavy drinking was associated with almost fivefold odds of developing CKD compared with their absence (odds ratio = 4.93, 95% CI: 2.45, 9.94). Smoking and consumption of four or more servings of alcohol per day are associated with CKD.
Problems concerning changes in the definition of urbanization for demographic analysis are examined. "This article attempts to examine the problem by clarifying the definition of the concept and indicators of urban and urbanization and by making a longitudinal analysis of urbanization using the Indonesian 1920-1990 Census data." (SUMMARY IN ENG)
This article describes and illustrates use of random-effects regression models (RRM) in relapse research. RRM are useful in longitudinal analysis of relapse data since they allow for the presence of missing data, time-varying or invariant covariates, and subjects measured at different timepoints. Thus, RRM can deal with "unbalanced" longitudinal relapse data, where a sample of subjects are not all measured at each and every timepoint. Also, recent work has extended RRM to handle dichotomous and ordinal outcomes, which are common in relapse research. Two examples are presented from a smoking cessation study to illustrate analysis using RRM. The first illustrates use of a random-effects ordinal logistic regression model, examining longitudinal changes in smoking status, treating status as an ordinal outcome. The second example focuses on changes in motivation scores prior to and following a first relapse to smoking. This latter example illustrates how RRM can be used to examine predictors and consequences of relapse, where relapse can occur at any study timepoint.
OBJECTIVE: Radiological status is an important objective endpoint in the assessment of ankylosing spondylitis (AS). We investigated the disease development of AS using radiological change. METHODS: The existing radiographs (n = 2,284) of 571 AS patients attending the Royal National Hospital for Rheumatic Diseases were scored retrospectively using the Bath Ankylosing Spondylitis Radiology Index. (1) Progression of disease was initially examined cross sectionally. Univariate analysis was used to examine factors associated with joint involvement. (2) Progression of disease was then examined longitudinally for patients with films at time of symptom onset. (3) Rate of progression of radiological change was calculated using longitudinal data of 2 sets of radiographs taken 10 years apart (patient number = 54). The results from this were used to extrapolate backwards to age at first radiological change. RESULTS: (1) Progression to cervical spine disease was a function of: disease duration, severity of hip and lumbar involvement, and a history of iritis (p < 0.001). Lumbar involvement was associated with disease duration, age now, and severity of cervical and hip involvement (p < 0.001). Hip involvement was a marker for cervical disease and associated with disease duration (p < 0.001). (2) Longitudinal analysis revealed marked variation among patients with a slow general rate of progression. (3) The progression of AS over any 10 year period is linear [first 10 years = 30% (SD 0.3) of potential change, 10-20 yrs = 40% (SD 0.3) change, 20-30 yrs = 35% (SD 0.4) change (p = 0.5)]. Backward extrapolation suggests that the approximate time of first radiological change is at the age of 8 years. CONCLUSION. (1) AS is a linearly progressive disease with about 35% change every 10 years. Spinal involvement is largely an expression of disease duration while the hips become involved in about 25% of individuals and may predict a more severe outcome for the cervical spine. (2) Backward extrapolation shows that the disease process may start as young as 8 years of age. However, the time interval between the disease trigger and radiological change remains unknown.
OBJECTIVE: Resistin is associated with insulin resistance in mice and may play a similar role in humans. The aim of our study was to examine the relationship of serum resistin level to body composition, insulin resistance, and related obesity phenotypes in humans. RESEARCH METHODS AND PROCEDURES: Sixty-four young (age 32 +/- 10 years), obese (BMI 32.9 +/- 5.6), nondiabetic subjects taking no medication, and 15 lean (BMI 21.1 +/- 1.3) volunteers were studied cross-sectionally. Thirty-five of the subjects were also reevaluated after 1.5 years on a weight reduction program entailing dieting and exercise; changes of serum resistin were compared with changes of BMI, body composition, fat distribution, and several indices of insulin sensitivity derived from plasma glucose and serum insulin levels measured during 75-g oral glucose tolerance test. RESULTS: In a cross-sectional analysis, serum resistin was significantly higher in obese subjects than in lean volunteers (24.58 +/- 12.93 ng/mL; n = 64 vs. 12.83 +/- 8.30 ng/mL; n = 15; p < 0.01), and there was a correlation between resistin level and BMI, when the two groups were combined (rho = 0.35, p < 0.01). Although cross-sectional analysis in obese subjects revealed no correlation between serum resistin and parameters related to adiposity or insulin resistance, longitudinal analysis revealed change in serum resistin to be positively correlated with changes in BMI, body fat, fat mass, visceral fat area, and mean glucose and insulin (rho = 0.39, 0.40, 0.44, 0.50, 0.40, and 0.50; p = 0.02, 0.03, 0.02, <0.01, 0.02, and <0.01, respectively). DISCUSSION: Resistin appears to be related to human adiposity and to be a possible candidate factor in human insulin resistance.
Plasma oxalate concentration was measured using an enzyme/bioluminescent assay in 289 patients (178 males, 111 females) with chronic renal failure (plasma creatinine greater than 200 mumol/l), age (SD) 55.5 (13.8) years. Plasma oxalate ranged between less than 0.8 and 48 mumol/l and showed a positive correlation with plasma creatinine (r = 0.57, p less than 0.0001). The slope of the regression line in 55 patients with glomerulonephritis (GN) was significantly lower than in patients with tubulointerstitial disease (TI); however the intercept was significantly higher in GN than in TI. Analysis of covariance showed no relationship between plasma oxalate concentration and age, duration of renal impairment, or administration of diuretics, vitamin D analogues, or phosphate binders. Longitudinal analysis of plasma oxalate measured 3-monthly in selected patients showed marked variability of oxalate/creatinine and oxalate/urea ratios.
OBJECTIVES: To evaluate the fetal cardiac time intervals from the longitudinal analysis of noninvasive fetal electrocardiography (fECG) in normal pregnancies. METHODS: One hundred singleton pregnancies were examined in this longitudinal study. Cardiac time intervals were derived from fetal electrocardiograms obtained noninvasively using three electrodes placed on the maternal abdomen. The variables measured included the durations of the P wave, PR interval, QRS complex, QT interval and T wave. RESULTS: Success rates for detecting the P, QRS and T waves were 74.6, 91.0 and 79.3%, respectively. Cardiac time intervals were significantly influenced by fetal age. The mean P-wave duration increased from 43.9 (18--22 weeks) to 52.9 ms (>/=37 weeks) (p < 0.001). PR intervals were 102.1 and 110.1 ms, for fetuses at 18 to 22 and >/=37 weeks (p < 0.001), respectively. QRS intervals were 47.2 and 52.6 ms (p < 0.001), while QT intervals were 224.0 and 242.7 ms (p < 0.001), at 18 to 22 and >/=37 weeks respectively. From 18 to 22 weeks to >/=37 weeks, QT(c) values increased from 343.8 to 367.7 ms (p < 0.001), while T-wave durations increased from 123.8 to 152.4 ms (p < 0.001). CONCLUSIONS: Serial noninvasive fECG of normal fetuses from 18 to 41 weeks of gestation show good success rates of fECG detection. Cardiac time intervals generally increased with increasing gestational age.
The aim of this study was to assess, in a prospective cohort of nurses, the risk factors associated with six back pain indicators: back pain (BP), chronic or recurring BP (occurring often or lasting for more than 3 months), cervical (CP), dorsal (DP) and lumbar (LP) pain and medical treatment for BP. In 1980, a sample of 469 nurses was randomly selected from six public sector hospitals. They were followed up and interviewed in 1980, 1985 and 1990. BP indicators were assessed on the basis of the nurses' self-reports during the 12 months before questionnaire administration in 1990. The data collected were subjected to cross-sectional analysis in 1990, to study the associations between the six BP indicators and the risk factors. In a longitudinal analysis, the 1990 BP indicators were analysed in relation to the risk factors present in 1985 among the 210 nurses who were still working in hospitals in 1990 and had not suffered from musculoskeletal disorders (MSDs) between 1980 and 1985. Of the 310 nurses still working in hospitals in 1990, 57.9% had suffered from BP within the previous 12 months, 23.6% of them from CP, 23.0% from DP and 41.1% from LP, 40.5% had suffered from chronic or recurring BP, 31.1% had undergone treatment and 7.4% had taken sick leave for BP. In 1990, BP accounted for 35.8% of the total number of days of sick leave.(ABSTRACT TRUNCATED AT 250 WORDS)