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Guillermo Marshall

Publications and source records attributed to Guillermo Marshall.

16 recordsLinked to original sources
PubMed2006

Non-linear random effects model for multivariate responses with missing data.

The use of random-effects models for the analysis of longitudinal data with missing responses has been discussed by several authors. In this paper, we extend the non-linear random-effects model for a single response to the case of multiple responses, allowing for arbitrary patterns of observed and missing data. Parameters for this model are estimated via the EM algorithm and by the first-order approximation available in SAS Proc NLMIXED. The set of equations for this estimation procedure is derived and these are appropriately modified to deal with missing data. The methodology is illustrated with an example using data coming from a study involving 161 pregnant women presenting to a private obstetrics clinic in Santiago, Chile.

Algorithms↗
PubMed2006

Non-linear random effects models with continuous time autoregressive errors: a Bayesian approach.

Measurements on subjects in longitudinal medical studies are often collected at several different times or under different experimental conditions. Such multiple observations on the same subject generally produce serially correlated outcomes. Traditional regression methods assume that observations within subjects are independent which is not true in longitudinal data. In this paper we develop a Bayesian analysis for the traditional non-linear random effects models with errors that follow a continuous time autoregressive process. In this way, unequally spaced observations do not present a problem in the analysis. Parameter estimation of this model is done via the Gibbs sampling algorithm. The method is illustrated with data coming from a study in pregnant women in Santiago, Chile, that involves the non-linear regression of plasma volume on gestational age.

Bayes Theorem↗
PubMed2006

Increased mortality from lung cancer and bronchiectasis in young adults after exposure to arsenic in utero and in early childhood.

Arsenic in drinking water is an established cause of lung cancer, and preliminary evidence suggests that ingested arsenic may also cause nonmalignant lung disease. Antofagasta is the second largest city in Chile and had a distinct period of very high arsenic exposure that began in 1958 and lasted until 1971, when an arsenic removal plant was installed. This unique exposure scenario provides a rare opportunity to investigate the long-term mortality impact of early-life arsenic exposure. In this study, we compared mortality rates in Antofagasta in the period 1989-2000 with those of the rest of Chile, focusing on subjects who were born during or just before the peak exposure period and who were 30-49 years of age at the time of death. For the birth cohort born just before the high-exposure period (1950-1957) and exposed in early childhood, the standardized mortality ratio (SMR) for lung cancer was 7.0 [95% confidence interval (CI), 5.4-8.9; p<0.001] and the SMR for bronchiectasis was 12.4 (95% CI, 3.3-31.7; p<0.001). For those born during the high-exposure period (1958-1970) with probable exposure in utero and early childhood, the corresponding SMRs were 6.1 (95% CI, 3.5-9.9; p<0.001) for lung cancer and 46.2 (95% CI, 21.1-87.7; p<0.001) for bronchiectasis. These findings suggest that exposure to arsenic in drinking water during early childhood or in utero has pronounced pulmonary effects, greatly increasing subsequent mortality in young adults from both malignant and nonmalignant lung disease.

Adult↗
PubMed2005

Time course of maternal plasma volume and hormonal changes in women with preeclampsia or fetal growth restriction.

We tested the hypothesis that women with idiopathic fetal growth restriction (FGR) or preeclampsia (PE) have lower concentrations of some water-retaining hormones, such as aldosterone and estradiol, either preceding or concomitant with the onset of the reduced plasma volume described in these women. Plasma volume and serum concentrations of estradiol, progesterone, and aldosterone were measured serially at monthly intervals in 135 pregnant women from week 10 until term. Twenty-three developed idiopathic FGR, 17 had PE, and 95 remained normotensive and delivered normal-size infants (controls). Changes over time for each variable were studied using mixed models. Maternal age, parity, and weight/height at term were similar in all of the groups. Birth weight, body length, and ponderal index were lower in FGR and PE than in controls. Plasma volume increased throughout pregnancy in controls but was lower in FGR and PE from week 14 to 17 until term. Aldosterone values were lower in PE from week 26 to 29 onwards and in FGR after week 34. Progesterone concentrations were higher in PE than either control or FGR from week 18 to 21 until term. In contrast, FGR pregnancies had reduced progesterone and estradiol concentrations after week 34. Progesterone:estradiol ratio was significantly higher only in the PE group. In mothers with idiopathic FGR or PE, less expansion in plasma volume occurred before alterations in hormonal concentrations. We speculate that the early rise in progesterone may have a pathogenic role in the development of preeclampsia.

Adult↗
PubMed2005

A new score for predicting neonatal very low birth weight mortality risk in the NEOCOSUR South American Network.

OBJECTIVE: To develop and validate a model for very low birth weight (VLBW) neonatal mortality prediction, based on commonly available data at birth, in 16 neonatal intensive care units (NICUs) from five South American countries. STUDY DESIGN: Prospectively collected biodemographic data from the Neonatal del Cono Sur (NEOCOSUR) Network between October 2000 and May 2003 in infants with birth weight 500 to 1500 g were employed. A testing sample and crossvalidation techniques were used to validate a statistical model for risk of in-hospital mortality. The new risk score was compared with two existing scores by using area under the receiver operating characteristic curve (AUC). RESULTS: The new NEOCOSUR score was highly predictive for in-hospital mortality (AUC=0.85) and performed better than the Clinical Risk Index for Babies (CRIB) and the NICHD risk models when used in the NEOCOSUR Network. The new score is also well calibrated - it had good predictive capability for in-hospital mortality at all levels of risk (HL test=11.9, p=0.85). The new score also performed well when used to predict in hospital neurological and respiratory complications. CONCLUSIONS: A new and relatively simple VLBW mortality risk score had a good prediction performance in a South American network population. This is an important tool for comparison purposes among NICUs. This score may prove to be a better model for application in developing countries.

Female↗
PubMed2004

Detection of lymphatic micrometastases in patients with stages I and II colorectal cancer: impact on five-year survival.

PURPOSE: Despite having removed the whole macroscopic disease (curative intent surgery), one of five patients with Stages I and II colorectal cancer will develop recurrence. Lymphatic micrometastases detected by immunohistochemistry could be one of explanation for recurrence and cancer-related death in patients without lymph node involvement at light microscopy. However, the biologic importance of micrometastases remains unclear. This study was designed to determine the impact of micrometastases in five-year survival in patients with Stages I and II colorectal cancer. METHODS: This retrospective study included patients operated on between May 1989 and January 1999 for colorectal cancer without histopathologic lymph node involvement. Patients who received any adjuvant therapy were excluded. Immunohistochemical staining of the lymph nodes was performed with antipancytokeratin antibodies. Follow-up data were obtained from the clinical database and death certificates. Survival was estimated by the Kaplan-Meier method and compared by the log-rank test. RESULTS: Micrometastases were observed in 26 of 90 patients (28.9 percent). The mean follow-up time was 90.7 (range, 11-160) months. Seventeen cancer-related deaths occurred during follow-up (18.9 percent), 6 of them in patients with micrometastases (23.1 percent) and 11 in patients without micrometastases (17.2 percent; P = 0.559). Cancer-specific five-year survival was 87 percent in the whole group and 81 percent in patients positive for micrometastases vs. 90 percent in negative patients ( P = 0.489). CONCLUSIONS: The presence of micrometastases in patients with Stages I and II colorectal cancer seems not to have any impact on cancer-specific survival.

Aged↗
PubMed2004

Bile acid synthesis is increased in Chilean Hispanics with gallstones and in gallstone high-risk Mapuche Indians.

BACKGROUND & AIMS: Gallstone disease is an important, costly health-care problem in Western societies. It is still unclear whether hepatic lipid regulatory enzymes play primary or secondary roles in gallstone formation. In this study, the aim was to investigate whether the synthesis of bile acids and cholesterol is increased in gallstone disease and to test whether such a metabolic change, if present, might occur before gallstone formation. METHODS: A total of 125 Chilean Hispanic women (80 without gallstones and 45 with gallstones) matched for age and body mass index were investigated, along with 40 Chilean Mapuche Indian women (20 without gallstones and 20 with gallstones), a population group in which the prevalence for gallstone disease is very high. Fasting blood plasma samples were assayed for 7 alpha-hydroxy-4-cholesten-3-one and lathosterol, 2 strong indicators for hepatic bile acid and body cholesterol synthesis, respectively. RESULTS: Plasma 7 alpha-hydroxy-4-cholesten-3-one levels, corrected for plasma cholesterol, were significantly increased by 50% in Hispanic women with gallstones as compared with gallstone-free Hispanics (P < 0.006). As compared with Hispanic women without gallstones, plasma 7 alpha-hydroxy-4-cholesten-3-one levels were increased by > or =100% (P < 0.002) in Mapuche Indian women, independently of whether gallstones were present. Plasma lathosterol, corrected for plasma cholesterol, was significantly increased by 22% in Hispanic women with gallstones and in Mapuche Indian women compared with Hispanic women. CONCLUSIONS: The results indicate that the synthesis of bile acids and cholesterol is induced in gallstone disease and precedes gallstone development. These inductions presumably occur as a response to an increased intestinal loss of bile acids.

Adult↗
PubMed2004

Relationship between processes of care and coronary bypass operative mortality and morbidity.

BACKGROUND: Information is limited regarding the effects of processes of care on cardiac surgical outcomes. Correspondingly, many recommended cardiac surgical processes of care are derived from animal experiments or clinical judgment. This report from the VA Cooperative Study in Health Services, "Processes, Structures, and Outcomes of Cardiac Surgery," focuses on the relationships between 3 process groups (preoperative evaluation, intraoperative care, and supervision by senior physicians) and a composite outcome, perioperative mortality and morbidity. METHODS: Data on 734 risk, process, and structure variables were collected prospectively on 3,988 patients who underwent coronary artery bypass grafting at 14 VA medical centers between 1992 and 1996. Data reduction was accomplished by examining data completeness and variation across sites and surgeon, using previously published data and clinical judgment. We then applied multivariable logistic regression to the 39 remaining processes of care to determine which were related to the composite outcome after adjusting for 17 patient-related risk factors and controlling for intraoperative complications. RESULTS: Our first analysis showed several measures of operative duration, the use of inotropic agents, transesophageal echo, lowest systemic temperature, and hemoconcentration/ultrafiltration, to be powerful predictors of the composite outcome. Because the use of inotropic agents and operative duration may be related to an intermediate outcome (eg, intraoperative complications), we performed a second analysis omitting these processes. The use of intraoperative transesophageal echo and hemoconcentration/ultrafiltration remained significantly associated with an increased risk of an event (odds ratios 1.60 and 1.36, respectively). CONCLUSIONS: Our results viewed in the context of past studies suggest the possibility that inotropic use, TEE, and hemoconcentration/ultrafiltration may have adverse effects on operative outcome. Further evaluation of these processes of care using observational data, as well as randomized trials when feasible, would be of interest.

Coronary Artery Bypass↗
PubMed2004

[Recent changes in prostate cancer mortality in Chile. Trends analysis from 1955 to 2001].

BACKGROUND: By the year 2000, prostate cancer became the second leading cause of cancer death in Chilean men of all ages and is the leading cause of cancer deaths in men of eighty years of age or older. AIM: To analyze the trends in mortality rates from prostate cancer in Chile in a fifty years series, estimating the rate of increase of such rates and their changes in time. MATERIAL AND METHODS: A trend analysis for age standardized mortality rates was performed, using join point regression analysis, which allows estimation of the annual percent change of rates and to find significant changes in such trend. RESULTS: Age standardized mortality rates in Chile reached their peak value in 1996, becoming apparently stable from then on. Crude rates have had a steady increase during the whole period. The trends analysis identified three different periods in the growth of the age standardized rates: a first one of slot increase in rates between 1955 and 1981 (0.9% annual increase), a second one of more aggressive growth starting in 1981 (2.6% annual increase), and a third period starting in 1996, in which rates slowly decline at an annual rate of 1%. CONCLUSIONS: The tendency of prostate cancer seen in Chile resembles that of industrialized countries, with an increase in its age standardized death rates that suffers a downturn by the end of the past decade. Besides early detection techniques, a substantial part of the reduction in mortality from prostate cancer could be explained by therapeutic improvements.

Age Distribution↗
PubMed2004

Effect of Mediterranean and Occidental diets, and red wine, on plasma fatty acids in humans. An intervention study.

The type of diet consumed by individuals has been associated with the development of some chronic diseases, including cardiovascular disease (CVD), cancer, diabetes, and others. Populations that consume diets rich in fruits and vegetables and drink wine in moderation, as the Mediterranean, have a higher life expectancy and less chronic diseases than other occidental populations. We carried out an intervention study in humans to evaluate the effect of a Mediterranean diet (MD), an Occidental diet (OD) and their supplementation with red wine, on biochemical, physiological and clinical parameters related to atherosclerosis and other chronic diseases. For 3 months, two groups of 21 male volunteers each, received either a MD or an OD; during the second month, red wine was added isocalorically, 240 ml/day. At days 0, 30, 60 and 90, clinical, physiological and biochemical evaluations were made. In this article we report on the results obtained in plasma fatty acids profile that includes saturated fatty acids (SFA), monounsaturated fatty acids (MUFA), polyunsaturated fatty acids (PUFA), omega-6 fatty acids, omega-3 fatty acids and omega-6/omega-3 ratio. Other results have been published previously. Plasma fatty acid percentages in the OD group, compared to the MD group, did not show differences in SFA, but the OD group showed lower levels of MUFA and omega-3 fatty acids, and higher levels of PUFA and omega-6 fatty acids, with a higher omega-6/omega-3 ratio than the MD group. Wine supplementation reduced MUFA and increased PUFA in both dietary groups, suggesting that wine could improve a diet with a good omega-6/omega-3 ratio. Volunteers on MD showed a better fatty acid profile than those on OD, suggesting a lower cardiovascular risk. Moderate consumption of wine improves this profile in the MD group.

Adult↗
PubMed2003

A comparison of single and combined visual, cytologic, and virologic tests as screening strategies in a region at high risk of cervical cancer.

Increased understanding of human papillomavirus (HPV) infection as the central cause of cervical cancer has permitted the development of improved screening techniques. To evaluate their usefulness, we evaluated the performance of multiple screening methods concurrently in a large population-based cohort of >8500 nonvirginal women without hysterectomies, whom we followed prospectively in a high-risk region of Latin America. Using Youden's index as a measure of the trade-off between sensitivity and specificity, we estimated the performances of a visual screening method (cervicography), conventional cytology, liquid-based cytology (ThinPrep), and DNA testing for 13 oncogenic HPV types. The reference standard of disease was neoplasia > or = cervical intraepithelial neoplasia grade 3 (CIN 3), defined as histologically confirmed CIN 3 detected within 2 years of enrollment (n=90) or invasive cancer detected within 7 years (n=20). We analyzed each technique alone and in paired combinations (n=112 possible strategies), and evaluated the significance of differences between strategies using a paired Z test that equally weighted sensitivity and specificity. As a single test, either liquid-based cytology or HPV DNA testing was significantly more accurate than conventional cytology or cervicography. Paired tests incorporating either liquid-based cytology or HPV DNA testing were not substantially more accurate than either of those two test strategies alone. However, a possibly useful synergy was observed between the conventional smear and cervicography. Consideration of age or behavioral risk profiles did not alter any of these conclusions. Overall, we conclude that highly accurate screening for cervical cancer and CIN 3 is now technically feasible. The remaining vital issue is to extend improved cervical cancer prevention programs to resource-poor regions.

Adolescent↗
PubMed2002

Prospective prediction in the presence of missing data.

A variety of methods and algorithms are available for estimating parameters in the class of a generalized linear model in the presence of missing values. However, there is little information on how this already built model can be used for prediction in new observations with missing data in the covariates. Dropping the observations with missing values is a widespread practice with serious statistical and non-statistical implications. One solution is to fit separate regression models, or submodels, to each pattern of missing covariates. In practice, for any iterative regression method, this approach is computationally intensive. We propose a simple methodology to predict outcomes for individuals with incomplete information based on the estimated coefficients and covariance from the already built model. This method does not require revisiting the original data set used to build the original model and works by generating a first-order approximation of any submodel coefficient estimates. This is achieved by using the SWEEP operator on an augmented covariance matrix obtained from the original model. We refer to this approach as the one-step sweep (OSS) method. The methodology is demonstrated using data from the Department of Veterans Affairs Continuous Improvement in Cardiac Surgery Program (CICSP). These data contain 30 day mortality, the outcome of interest, and risk information for over 14,000 patients who underwent coronary artery bypass grafting (CABG) surgery over a four-year period. Using complete data from the first 3.5 years of this study period, a logistic regression model was built. This model was then used to predict mortality for patients undergoing CABG in the most recent 6-months. In order to evaluate the performance of the OSS method we randomly generated observations with missing covariates in the 6-month prediction database. We use this simulation to demonstrate that the computationally efficient OSS substantially reduces the error in risk-adjusted mortality created when cases with incomplete information are eliminated. Lastly, we derive the relationship between the OSS method and data imputation.

Computer Simulation↗
PubMed2002

[Natural history of cholelithiasis and incidence of cholecystectomy in an urban and a Mapuche rural area].

BACKGROUND: Cholelithiasis is the second cause of hospital admissions in Chile. AIM: To study the prevalence of symptomatic gallstone disease and opportunity of cholecystectomy in La Florida, Santiago and among Mapuche Indians in Huapi Island. PATIENTS AND METHODS: In the period 2000-2001, we contacted to 71% (1127 subjects) and to 61% (145 subjects) patients of La Florida and Huapi Island, respectively, that had previously participated in an epidemiological study on cholelithiasis in 1993. We defined symptomatic gallstone patients as those with a history of biliary colic. Each patient was subjected to gallbladder ultrasound. RESULTS: In 1993, 30-35% of gallstone patients were symptomatic (approximately 70% women). During the lapse 1993-2001, only 50% of subjects from La Florida and 25% of patients from Huapi Island were cholecystectomized (p < 0.05). Fifty percent of cholecystectomies were emergency operations. In 38 symptomatic Mapuche Indians from Huapi, cholecystectomy was indicated in 2001. After five months of the indication, only one of these subjects had been operated. Laparoscopic cholecystectomy represented 40% of all cholecystectomies performed in the National Health Service Hospitals. CONCLUSIONS: This study demonstrates an unacceptable high prevalence of symptomatic gallstone patients remaining non-operated in both the urban and rural communities. This reciprocally correlates with the high frequency of emergency cholecystectomies and the high incidence of gallbladder cancer among Chileans. This study contrasts negatively with the situation of Scotland, where 73.5% of cholecystectomies were laparoscopic in 1998-1999. To reach Scotland standards, the Chilean Public Health System should increase the number of cholecystectomies from 27,000 in 2001 to 57,510

Adult↗
PubMedDate not supplied

Raloxifene is a better antioxidant of low-density lipoprotein than estradiol or tamoxifen in postmenopausal women in vitro.

OBJECTIVE: The oxidation of low-density lipoprotein (LDL) is an important factor in the development of atherosclerosis. The antioxidant activity of some compounds buffers the free radicals generated either endogenously or exogenously, thus decreasing the potential damage mediated by oxidation. Estrogens are potent antioxidants of LDL, in vitro and in vivo, a mechanism that could probably influence the cardioprotection associated with hormone replacement therapy in postmenopause. We conducted an in vitro study of the antioxidant effect on LDL of two selective estrogen receptor modulators, raloxifene (RLX) and tamoxifen (TMX), comparing them with the known antioxidant effect of estradiol (E2 ). DESIGN: LDL was isolated by ultracentrifugation from plasma obtained from 12 healthy, untreated, postmenopausal women. Aliquots containing 0.5 mg of LDL protein were incubated for 4 h with CuSO4 (15 micro M) to induce oxidative stress and with one of the three compounds studied: RLX, TMX, or E2 at doses of 0, 1, 2, 3, 5, 15, 50, and 500 micro M, and 1 and 2 mM. Malonaldehyde (MDA, nmol/mg protein) was measured as a marker of LDL oxidation. RESULTS: E2 induced a dose-dependent decrease in MDA concentration. MDA values decreased significantly, as compared with baseline, starting at a concentration of 2 micro M for RLX and 3 micro M for both, TMX, or E2. The dose necessary to reduce the generation of MDA by 50% was significantly lower for RLX (3.3 micro M, < 0.001) than for E2 (24.6 micro M ) or TMX (35.3 micro M). The area under the curve also showed a higher antioxidant activity for RLX compared with TMX or E2 ( < 0.001). CONCLUSIONS: The in vitro antioxidant activity of RLX is substantially more potent than TMX or E2. This finding, added to the other beneficial effects of the drug in the cardiovascular system, could imply some cardioprotector effect.

Antioxidants↗
PubMedDate not supplied

[An assessment of the severity, proportionality and risk of mortality of very low birth weight infants with fetal growth restriction. A multicenter South American analysis].

OBJECTIVES: To evaluate the clinical severity and proportionality of small for gestational age, very low birth weight neonates (< 1,500 g) and to estimate the neonatal mortality risk associated with the condition of being small for gestational age according to the degree of severity and proportionality. METHODS: Observational design. All of the NEOCOSUR Collaborative Group's very low birth weight infants (25-36 weeks' gestation) were included (n = 1,518). Anthropometric indices: birth weight < 3rd and 10th percentile. Severity (fetal growth ratio = observed weight/mean birth weight for gestational age); no growth restriction: fetal growth ratio 0.90-1.10, mild: fetal growth ratio 0.80-0.89, moderate: fetal growth ratio 0.75-0.79 and severe: fetal growth ratio < 0.75. Proportionality: coefficient of bimodality and z score for ponderal index (PI = g/cm3 x 100). Neonatal mortality until discharge. RESULTS: < 3rd percentile: 13.5% (p < 0.001); < 10th percentile: 31% (p < 0.001); fetal growth ratio: 0.90-/+0.21 (p < 0.001), mild restriction: 20.8%, moderate restriction: 8.7% and severe restriction: 32.6%. Coefficient of bimodality: 0.53; PI z score < -1: 8%. Maternal hypertensive disease was systematically associated with being small for gestational age (aOR 1.20, 95% CI 0.86-1.67), fetal growth ratio < or = 0.89 (aOR 1.71, 1.24-2.36) and PI z score < -1 (aOR 1.60, 1.03-2.41). Adjusted odds ratios for neonatal mortality were: 2.64 (95% CI 1.71-3.92) for being small for gestational age, 2.76 (95% CI 1.85-4.10) for fetal growth ratio < or = 0.89, and 1.37 (95% CI 0.80-2.32) for z score PI < -1. CONCLUSIONS: Small for gestational age, mostly symmetric and severe restriction is a frequent condition in < 1,500 g neonates and is associated with higher mortality rates.

Anthropometry↗