Biomarker circadian rhythm profiles in critically ill mechanically ventilated patients

Objective: To explore the natural trajectory of core body temperature (CBT) and cortisol (CORT) circadian rhythms in mechanically ventilated intensive care unit (MV ICU) patients. ^ Design: Prospective, observational, time-series pilot study. ^ Setting: Medical-surgical and pulmonary ICUs in a tertiary care hospital. ^ Sample: Nine (F = 3, M = 6) adults who were mechanically ventilated within 12 hrs of ICU admission with mean ± SD age of 65.2 ± 14 years old. ^ Measurements: Core body temperature and environmental measures of light, sound, temperature, and relative humidity were logged in 1-min intervals. Hourly urine specimens and 2-hr interval blood specimens were collected for up to 7 consecutive days for CORT assay. Mechanical ventilation days, ICU length of stay, and ICU mortality were documented. Acute Physiology and Chronic Health Evaluation (APACHE) II scores were computed for each study day. The data of each biologic and environmental variable were analyzed using single cosinor analysis of 24-hr serial segments. One patient did not complete the study because mortality occurred within 8 hrs of enrollment. Nine ICU patients completed the study in 1.6 to 7.0 days. ^ Results: No normal circadian rhythm pattern was found when the cosinor-derived parameters of amplitude (one-half the peak-trough variability) and acrophase (peak time) were compared with cosinor-derived parameter reference ranges of healthy, diurnally active humans, although 83% of patient-day CBT segments showed statistically significant (p ≤ .05) and biologically meaningful (R2≥ 0.30) 24-hr rhythms with abnormal cosinor parameters. Cosinor parameters of the environmental temporal profiles showed 27% of light, 76% of ambient temperature, and 78% of relative humidity serial segments had a significant and meaningful 24-hr diurnal pattern. Average daily light intensity varied from 34 to 187 lx with a maximum light exposure of 1877 lx. No sound measurement segment had a statistically significant cosine pattern, and numerous 1-minute interval peaks ≥ 60 dB occurred around the clock. Average daily ambient temperature and relative humidity varied from 19 to 24°C and from 25% to 61%, respectively. There was no statistically significant association between CBT or clinical outcomes and cosinor-derived parameters of the environmental variables. Circadian rhythms of urine and plasma CORT were deferred for later analysis. ^ Conclusions: The natural trajectory of the CBT circadian rhythm in MV ICU patients demonstrated persistent cosinor parameter alteration, even when a significant and meaningful 24-hr rhythm was present. The ICU environmental measures showed erratic light and sound exposures. Room temperature and relative humidity data produced the highest rate of significant and meaningful diurnal 24-hr patterns. Additional research is needed to clarify relations among the CBT biomarker of the circadian clock and environmental variables of MV ICU patients. ^

RELATION OF TYPE OF REPORTED ILLNESSES TO PATTERN OF USE OF THE STUDENT HEALTH CENTER BY THE INTERNATIONAL STUDENTS AT TEXAS SOUTHERN UNIVERSITY, HOUSTON, TEXAS

The state of knowledge on the relation of stress factors, health problems and health service utilization among university students is limited. Special problems of stress exist for the international students due to their having to adjust to a new environment. It is this latter problem area that provides the focus for this study. Recognizing there are special stress factors affecting the international students, it is first necessary to see if the problems of cultural adaptation affect them to any greater degree than American students attending the same university.^ To make the comparison, the study identified a number of health problems of both American and international students and related their frequency to the use of the Student Health Center. The expectation was that there would be an association between the number of health problems and the number of life change events experienced by these students and between the number of health problems and stresses from social factors. It was also expected that the number of health problems would decline with the amount of social support.^ The population chosen were students newly enrolled in Texas Southern University, Houston, Texas in the Fall Semester of 1979. Two groups were selected at random: 126 international and 126 American students. The survey instrument was a self-administered questionnaire. The response rate was 90% (114) for the international and 94% (118) for the American students.^ Data analyses consisted of both descriptive and inferential statistics. Chi-squares and correlation coefficients were the statistics used in comparing the international students and the American students.^ There was a weak association between the number of health problems and the number of life change events, as reported by both the international and the American students. The study failed to show any statistically significant association between the number of stress from social factors and the number of health problems. It also failed to show an association between the number of health problems and the amount of social support. These findings applied to both the international and the American students.^ One unexpected finding was that certain health problems were reported by more American than international students. There were: cough, diarrhea, and trouble in sleeping. Another finding was that those students with health insurance had a higher level of utilization of the Health Center than those without health insurance. More international than American students utilized the Student Health Center.^ In comparing the women students, there was no statistical significant difference in their reported fertility related health problems.^ The investigator recommends that in follow-up studies, instead of grouping all international students together, that they be divided by major nationalities represented in the student body; that is, Iranians, Nigerians and others. ^

A case-comparison interview study of brain tumors and employment in occupations with presumed electric and magnetic field exposures

Results from epidemiologic studies suggest that persons working in occupations with presumed electric and magnetic field (EMF) exposures are at increased risk of brain cancer. This study utilized data from a completed, population-based, interview case-control study of central nervous system (CNS) tumors and employment in the petrochemical industry to test the hypothesis that employment in EMF-related occupations increases CNS tumor risk. A total of 375 male residents of the Texas-Louisiana Gulf Coast Area, age 20 to 79, with primary neuroglial CNS tumors diagnosed during the period 1980-84 were identified. A population-based comparison group of 450 age, race and geographically matched males was selected. Occupational histories and potential risk factor data were collected via personal interviews with study subjects or their next-of-kin.^ Adjusted odds ratios were less than 1.0 for persons ever employed in an electrical occupation (OR = 0.65; 95% CI = 0.40-1.09) or whose usual occupation was electrical (OR = 0.76; 95% CI = 0.33-1.73). Relative risk estimates did not increase significantly as time since first employment or duration of employment increased. Examination of CNS tumor risk by high (OR = 0.80), medium (OR = 0.88) and low (OR = 0.45) exposure categories for persons whose usual occupation was electrical did not indicate a dose-response pattern. In addition, the mean age of exposed cases was not significantly younger than that for unexposed cases. Analysis of risk by probability of exposure to EMFs showed non-significant elevations in the adjusted odds ratio for definite exposed workers defined by their usual occupation (OR = 1.78; 95% CI = 0.70-4.51) and ever/never employed status (OR = 1.54; 95% CI = 0.17-4.91).^ These findings suggest that employment in occupations with presumed EMF exposures does not increase CNS tumor risk as was suggested by previous investigations. The results of this study also do not support the EMF-tumor promotion hypothesis. ^

A simulation study using the hybrid statistic and the meta-analysis t-test for data with matched and unmatched subjects in the interim analysis of clinical trials

An interim analysis is usually applied in later phase II or phase III trials to find convincing evidence of a significant treatment difference that may lead to trial termination at an earlier point than planned at the beginning. This can result in the saving of patient resources and shortening of drug development and approval time. In addition, ethics and economics are also the reasons to stop a trial earlier. In clinical trials of eyes, ears, knees, arms, kidneys, lungs, and other clustered treatments, data may include distribution-free random variables with matched and unmatched subjects in one study. It is important to properly include both subjects in the interim and the final analyses so that the maximum efficiency of statistical and clinical inferences can be obtained at different stages of the trials. So far, no publication has applied a statistical method for distribution-free data with matched and unmatched subjects in the interim analysis of clinical trials. In this simulation study, the hybrid statistic was used to estimate the empirical powers and the empirical type I errors among the simulated datasets with different sample sizes, different effect sizes, different correlation coefficients for matched pairs, and different data distributions, respectively, in the interim and final analysis with 4 different group sequential methods. Empirical powers and empirical type I errors were also compared to those estimated by using the meta-analysis t-test among the same simulated datasets. Results from this simulation study show that, compared to the meta-analysis t-test commonly used for data with normally distributed observations, the hybrid statistic has a greater power for data observed from normally, log-normally, and multinomially distributed random variables with matched and unmatched subjects and with outliers. Powers rose with the increase in sample size, effect size, and correlation coefficient for the matched pairs. In addition, lower type I errors were observed estimated by using the hybrid statistic, which indicates that this test is also conservative for data with outliers in the interim analysis of clinical trials.^

Frequencies and risk factors for bisphosphonate-related osteonecrosis of the jaw in cancer patients: A matched case-control study

Bisphosphonates represent a unique class of drugs that effectively treat and prevent a variety of bone-related disorders including metastatic bone disease and osteoporosis. High tolerance and high efficacy rates quickly ranked bisphosphonates as the standard of care for bone-related diseases. However, in the early 2000s, case reports began to surface that linked bisphosphonates with osteonecrosis of the jaw (ONJ). Since that time, studies conducted have corroborated the linkage. However, as with most disease states, many factors can contribute to the onset of disease. The aim of this study was to determine which comorbid factors presented an increased risk for developing ONJ in cancer patients.^ Using a case-control study design, investigators used a combination of ICD-9 codes and chart review to identify confirmed cases of ONJ at The University of Texas M. D. Anderson Cancer Center (MDACC). Each case was then matched to five controls based on age, gender, race/ethnicity, and primary cancer diagnosis. Data querying and chart review provided information on variables of interest. These variables included bisphosphonate exposure, glucocorticoids exposure, smoking history, obesity, and diabetes. Statistical analysis was conducted using PASW (Predictive Analytics Software) Statistics, Version 18 (SPSS Inc., Chicago, Illinois).^ One hundred twelve (112) cases were identified as confirmed cases of ONJ. Variables were run using univariate logistic regression to determine significance (p < .05); significant variables were included in the final conditional logistic regression model. Concurrent use of bisphosphonates and glucocorticoids (OR, 18.60; CI, 8.85 to 39.12; p < .001), current smokers (OR, 2.52; CI, 1.21 to 5.25; p = .014), and presence of diabetes (OR, 1.84; CI, 1.06 to 3.20; p = .030) were found to increase the risk for developing ONJ. Obesity was not associated significantly with ONJ development.^ In this study, cancer patients that received bisphosphonates as part of their therapeutic regimen were found to have an 18-fold increase in their risk of developing ONJ. Other factors included smoking and diabetes. More studies examining the concurrent use of glucocorticoids and bisphosphonates may be able to strengthen any correlations.^