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PubMed2007

The excess medical cost and health problems of family members of persons diagnosed with alcohol or drug problems.

BACKGROUND: Having a family member with substance use problems affects family functioning, which may lead to increased medical problems and increased health care utilization and costs in the other family members. AIM: We sought to estimate the excess medical costs and prevalence of diagnosed health conditions of family members of persons with an alcohol or drug diagnosis (AOD) compared with the family members of similar persons without an AOD. METHODS: Using a large health plan's administrative databases, we identified persons who received an AOD between 2001 and 2004 and a similar group of persons with no AOD during that time. Using a hierarchical linear mixed model, we compared the cost and utilization of the family members of the AOD and non-AOD patients in the 2 years prior to the AOD patient's first AOD. Using logistic regression, we determined whether the family members of patients with AODs were more likely than comparison family members to be diagnosed with medical conditions. RESULTS: Family members of patients with AODs had greater health care costs than comparison family members in the second year before the index date (490 dollars) and in the year before the index date (433 dollars). This was the case for both adult and child family members. They also were more likely to be diagnosed with many medical conditions, especially substance abuse and depression. CONCLUSIONS: Family members of patients with AODs have greater health care costs and are more likely to be diagnosed with a number of medical conditions than family members of similar persons without an AOD.

Adolescent↗

PubMedDate not supplied

Symptom profile of multiple chemical sensitivity in actual life.

OBJECTIVE: This study was conducted to confirm the definition of multiple chemical sensitivity (MCS) in actual life: that multiple symptoms are provoked in multiple organs by exposure to, and ameliorated by avoidance of, multiple chemicals at low levels. We used the Ecological Momentary Assessment to monitor everyday symptoms and the active sampling and passive sampling methods to measure environmental chemical exposure. METHODS: Eighteen patients with MCS, diagnosed according to the 1999 consensus criteria, and 12 healthy controls participated in this study. Fourteen patients and 12 controls underwent 1-week measurement of physical and psychologic symptoms and of the levels of exposure to various chemicals. Linear mixed models were used to test the hypotheses regarding the symptom profile of MCS patients. RESULTS: Some causative chemicals were detected in 11 of 14 MCS patients. Two other patients did not report any hypersensitivity episodes, whereas passive sampling showed far less exposure to chemicals than control subjects. Another subject reported episodic symptoms but was excluded from the following analyses because no possible chemical was detected. Eleven of the 17 physical symptoms and all four mood subscales examined were significantly aggravated in the interview based on "patient-initiated symptom prompts." On the other hand, there were no differences in physical symptoms or mood subscales between MCS patients and control subjects in the interview based on "random prompts." CONCLUSIONS: MCS patients do not have either somatic or psychologic symptoms under chemical-free conditions, and symptoms may be provoked only when exposed to chemicals.

Adult↗

PubMed2006

Predictors of hepatitis C virus RNA levels in a prospective cohort study of drug users.

High levels of hepatitis C virus (HCV) RNA are associated with a poor response to treatment of chronic hepatitis C, and a substantial reduction in HCV RNA levels predicts a favorable treatment response. We prospectively studied time-dependent and time-independent predictors of HCV RNA levels in 264 drug users with chronic HCV infection. Interviews on medical history and high-risk behaviors, phlebotomy for HIV viral load, serum HCV RNA levels as measured by the COBAS Amplicor HCV Monitor (Roche Diagnostics, Branchburg, NJ), and a lymphocyte subset assay were performed. Factors associated with HCV RNA levels over time were analyzed using a linear mixed model. Nearly 70% of the participants were men, two thirds were Hispanic, and the mean age was 46 years. HCV RNA levels increased over time. Older age (P < 0.001), HIV seropositivity (P = 0.03), and HCV nongenotype 1 (P = 0.05) were predictors of higher HCV RNA levels on multivariate analysis. Among 142 HIV-seropositive participants, a detectable HIV-1 viral load (P < 0.001) and recent alcohol use (P = 0.02) were predictors of higher HCV RNA levels. The predictors of higher HCV RNA levels found in this longitudinal study are consistent with those of prior cross-sectional studies. Further studies are warranted to determine if treatment of alcohol use affects HCV RNA levels.

Adult↗

PubMed2006

Tissue-specific associations between mitochondrial DNA levels and current treatment status in HIV-infected individuals.

BACKGROUND: Tissue mitochondrial DNA (mtDNA) levels have been proposed as a marker of nucleoside analouge reverse transcriptase inhibitor (NRTI) toxicity. However, clinical studies have yielded conflicting data regarding possible associations with mtDNA levels. This study examined mtDNA levels in matched samples of peripheral blood mononuclear cells (PBMCs) and subcutaneous fat from a large Australian cohort to examine treatment, clinical, and demographic associations with mtDNA depletion. METHODS: mtDNA was quantified by real-time polymerase chain reaction. Results were compared across patient treatment and demographic details using linear mixed models. RESULTS: One hundred sixty-three PBMCs and 161 fat samples were available from 61 individuals. Current NRTI exposure was the major determinant of mtDNA levels. Both ddI (didanosine) and d4T (stavudine) exposures were associated with mtDNA depletion in fat (P < or = 0.0001 vs. those not on NRTIs). DdI exposure (P = 0.003), but not d4T exposure (P = 0.5), was associated with mtDNA depletion in PBMCs. No association between patient demographics or time on current therapy and mtDNA was observed. CONCLUSIONS: Current NRTI exposure is the major determinant of tissue mtDNA, but the precise determinants are tissue specific. Both ddI and d4T exposure are associated with fat mtDNA depletion, whereas ddI exposure was the only observed association with mtDNA depletion in PBMCs.

Adult↗

PubMed2004

Effect of triolein emulsion on the blood-testis barrier in cats.

PURPOSE: Although the blood-testis barrier (BTB) is beneficial physiologically, it acts as an obstacle to chemotherapy. We wished to determine whether a triolein emulsion could alter the permeability of the BTB in cats. MATERIALS AND METHODS: An emulsion of 0.05-mL triolein in 20 mL of saline was infused into the abdominal aorta just proximal to the branching of the renal arteries of each of 15 cats (embolic group). As controls, 12 cats were each similarly infused with 20 mL of normal saline (control group). Pre and postcontrast MR images were obtained 30 minutes and 2 hours after embolization. The images were analyzed for the presence and degree of contrast enhancement (qualitative analysis), and the contrast enhancement ratios (CER) derived from one testis of each animal were compared and statistically analyzed by the mixed linear model (quantitative analysis). RESULTS: Contrast enhancement of the testis was observed in both groups at both time points, but it was more prominent in the embolic group. The CERs in the embolic group (0.63 at 30 minutes, 0.42 at 2 hours) were significantly higher than in the control group (0.36 at 30 minutes, 0.28 at 2 hours; P = 0.0001). In each group, the CERs at 2 hours were significantly lower than those at 30 minutes (P = 0.006). CONCLUSION: Intra-arterial infusion of triolein emulsion increased the permeability of the BTB. This result may be useful in future studies of BTB disruptions caused by fat emulsions.

Animals↗

PubMed2007

Diurnal variation of central corneal thickness and Goldmann applanation tonometry estimates of intraocular pressure.

PURPOSE: To determine whether there is a temporal relationship between the diurnal variation of central corneal thickness (CCT) and intraocular pressure (IOP) by Goldmann applanation tonometry in young normal human participants in vivo. METHODS: Twenty-five eyes of 25 young healthy normal participants were examined in a prospective observational cross-sectional study. IOP, CCT and corneal curvature were measured using standard clinical techniques over a 24-hour period, and the temporal interrelationships between these parameters were examined. RESULTS: The overnight change in IOP measured by Goldmann tonometry was 3.1+/-2.4 mm Hg (P<0.001), CCT was 20.1+/-10.9 mum (P=0.016), with no statistical change in central corneal curvature (0.05 mm, P=0.477, paired t test with Bonferroni correction). Both IOP and CCT were highest on awakening at 7:00 then dropped rapidly to baseline levels by 9:00 (linear mixed models), and these two parameters were highly correlated (r=0.978, P<0.001). After 9:00, there was no correlation between these parameters (r=-0.453, P=0.260). CONCLUSIONS: The results of this study have highlighted a potential link between the diurnal variation of CCT and the accuracy of Goldmann tonometry estimates of IOP during the first 2 hours after awakening. Clinicians should be wary of using Goldmann tonometry to estimate IOP until the overnight increase in CCT has resolved.

Adolescent↗

PubMed2026

Willingness to switch to long-acting regimens among people with HIV: a systematic review and meta-analysis.

OBJECTIVES: Long-acting regimens (LARs) offer promising alternatives for people with HIV, enhancing autonomy and convenience. Understanding preferences for LAR is essential to guide policy and implementation. DESIGN: This systematic review and meta-analysis examined willingness among adults with HIV to switch from daily oral antiretroviral therapy (ART) to LAR. METHODS: Following PRISMA guidelines, we included studies of adults with HIV using daily oral ART reporting willingness to switch to existing or hypothetical LAR. The primary outcome was the proportion willing to switch. Articles were searched in PubMed and Embase up to October 2024. Risk of bias was assessed using the RoB-PrevMH tool. A random-effects meta-analysis with a generalized linear mixed model synthesized willingness for LAR. Subgroup analyses explored heterogeneity. Alternative LAR were summarized descriptively. RESULTS: Searches identified 2038 records, of which 22 studies were included. Most studies were conducted in Europe or North America (96%). Willingness to switch to any LAR was 70% [95% confidence interval (95% CI): 59-79; I2  = 97.9%]. Furthermore, two-monthly intramuscular injections were the most frequently investigated LAR, with a pooled willingness of 60% (95%CI: 42-76; I2  = 97.5%). No study-level characteristics explained heterogeneity. Limited studies investigated willingness for alternative LAR. CONCLUSION: The majority of people with HIV expressed willingness to switch to LAR, with two-monthly intramuscular injections being the most commonly investigated formulation. Substantial heterogeneity persisted, suggesting that LAR preferences are highly context dependent. Evidence on alternative LAR, including tablets, implants and intravenous infusions, is limited. Low and middle-income countries were underrepresented, highlighting the need for geographically diverse research to better understand context-specific preferences and thereby inform treatment policy.

Humans↗

PubMed2003

Photosynthetic acclimation is reflected in specific patterns of gene expression in drought-stressed loblolly pine.

Because the product of a single gene can influence many aspects of plant growth and development, it is necessary to understand how gene products act in concert and upon each other to effect adaptive changes to stressful conditions. We conducted experiments to improve our understanding of the responses of loblolly pine (Pinus taeda) to drought stress. Water was withheld from rooted plantlets of to a measured water potential of -1 MPa for mild stress and -1.5 MPa for severe stress. Net photosynthesis was measured for each level of stress. RNA was isolated from needles and used in hybridizations against a microarray consisting of 2173 cDNA clones from five pine expressed sequence tag libraries. Gene expression was estimated using a two-stage mixed linear model. Subsequently, data mining via inductive logic programming identified rules (relationships) among gene expression, treatments, and functional categories. Changes in RNA transcript profiles of loblolly pine due to drought stress were correlated with physiological data reflecting photosynthetic acclimation to mild stress or photosynthetic failure during severe stress. Analysis of transcript profiles indicated that there are distinct patterns of expression related to the two levels of stress. Genes encoding heat shock proteins, late embryogenic-abundant proteins, enzymes from the aromatic acid and flavonoid biosynthetic pathways, and from carbon metabolism showed distinctive responses associated with acclimation. Five genes shown to have different transcript levels in response to either mild or severe stress were chosen for further analysis using real-time polymerase chain reaction. The real-time polymerase chain reaction results were in good agreement with those obtained on microarrays.

Acclimatization↗

PubMed2004

Interaction-dependent gene expression in Mla-specified response to barley powdery mildew.

Plant recognition of pathogen-derived molecules influences attack and counterattack strategies that affect the outcome of host-microbe interactions. To ascertain the global framework of host gene expression during biotrophic pathogen invasion, we analyzed in parallel the mRNA abundance of 22,792 host genes throughout 36 (genotype x pathogen x time) interactions between barley (Hordeum vulgare) and Blumeria graminis f. sp hordei (Bgh), the causal agent of powdery mildew disease. A split-split-plot design was used to investigate near-isogenic barley lines with introgressed Mla6, Mla13, and Mla1 coiled-coil, nucleotide binding site, Leu-rich repeat resistance alleles challenged with Bgh isolates 5874 (AvrMla6 and AvrMla1) and K1 (AvrMla13 and AvrMla1). A linear mixed model analysis was employed to identify genes with significant differential expression (P value < 0.0001) in incompatible and compatible barley-Bgh interactions across six time points after pathogen challenge. Twenty-two host genes, of which five were of unknown function, exhibited highly similar patterns of upregulation among all incompatible and compatible interactions up to 16 h after inoculation (hai), coinciding with germination of Bgh conidiospores and formation of appressoria. By contrast, significant divergent expression was observed from 16 to 32 hai, during membrane-to-membrane contact between fungal haustoria and host epidermal cells, with notable suppression of most transcripts identified as differentially expressed in compatible interactions. These findings provide a link between the recognition of general and specific pathogen-associated molecules in gene-for-gene specified resistance and support the hypothesis that host-specific resistance evolved from the recognition and prevention of the pathogen's suppression of plant basal defense.

Carrier Proteins↗

PubMed2005

Non-Gaussian smoothing of low-count transmission scans for PET whole-body studies.

A non-Gaussian smoothing (NGS) technique is developed for filtering low count transmission (TR) data to be used for attenuation correction (AC) of positron emission tomography (PET) studies. The method is based on a statistical technique known as the generalized linear mixed model that allows an inverse link function that avoids the inversion of the observed transmission data. The NGS technique has been implemented in the sinogram domain in one-dimensional mode as angle-by-angle computation. To make it adaptive as a function of the TR count statistics we also develop and validate an objective procedure to choose an optimal smoothing parameter. The technique is assessed using experimental phantoms, simulating PET whole-body studies, and applied to real patient data. Different experimental conditions, in terms of TR scan time (from 1 h to 1 min), covering a wide range of TR counting statistic are considered. The method is evaluated, in terms of mean squared error (MSE), by comparing pixel by pixel the distribution for high counts statistics TR scan (1 h) with the corresponding counts distribution for low count statistics TR scans (e.g., 1 min). The smoothing parameter selection is shown to have high efficiency, meaning that it tends to choose values close to the unknown best value. Furthermore, the counts distribution of emission (EM) images, reconstructed with AC generated using low count TR data (1 min), are within 5% of the corresponding EM images reconstructed with AC generated using the high count statistics TR data (1 h). An application to a real patient whole-body PET study shows the promise of the technique for routine use.

Algorithms↗

PubMed2003

Fisher Lecture: the 2002 R. A. Fisher lecture: dedicated to the memory of Shanti S. Gupta. Variances are not always nuisance parameters.

In classical problems, e.g., comparing two populations, fitting a regression surface, etc., variability is a nuisance parameter. The term "nuisance parameter" is meant here in both the technical and the practical sense. However, there are many instances where understanding the structure of variability is just as central as understanding the mean structure. The purpose of this article is to review a few of these problems. I focus in particular on two issues: (a) the determination of the validity of an assay; and (b) the issue of the power for detecting health effects from nutrient intakes when the latter are measured by food frequency questionnaires. I will also briefly mention the problems of variance structure in generalized linear mixed models, robust parameter design in quality technology, and the signal in microarrays. In these and other problems, treating variance structure as a nuisance instead of a central part of the modeling effort not only leads to inefficient estimation of means, but also to misleading conclusions.

Analysis of Variance↗

PubMed2000

The analysis of group truncated binary data with random effects: injury severity in motor vehicle accidents.

The analysis of group truncated binary data has been previously considered by O'Neill and Barry (1995b, Biometrics 51, 533-541), where the analysis assumed that responses within each group were independent. In this paper, we consider the analysis of such data when there is group-level heterogeneity. A generalized linear mixed model is hypothesized to model the response and maximum likelihood estimates are derived for the truncated case. A score test is derived to test for heterogeneity. Finally, the method is applied to a set of traffic accident data.

Accidents, Traffic↗

PubMed2000

Effects of covariate measurement error in the initial level and rate of change of an exposure variable.

When repeated measures of an exposure variable are obtained on individuals, it can be of epidemiologic interest to relate the slope of this variable over time to a subsequent response. Subject-specific estimates of this slope are measured with error, as are corresponding estimates of the level of exposure, i.e., the intercept of a linear regression over time. Because the intercept is often correlated with the slope and may also be associated with the outcome, each error-prone covariate (intercept and slope) is a potential confounder, thereby tending to accentuate potential biases due to measurement error. Under a familiar mixed linear model for the exposure measurements, we present closed-form estimators for the true parameters of interest in the case of a continuous outcome with complete and equally timed follow-up for all subjects. Generalizations to handle incomplete follow-up, other types of outcome variables, and additional fixed covariates are illustrated via maximum likelihood. We provide examples using data from the Multicenter AIDS Cohort Study. In these examples, substantial adjustments are made to uncorrected parameter estimates corresponding to the health-related effects of exposure variable slopes over time. We illustrate the potential impact of such adjustments on the interpretation of an epidemiologic analysis.

Acquired Immunodeficiency Syndrome↗

PubMed2000

Estimation of individual genetic effects from binary observations on relatives applied to a family history of respiratory illnesses and chronic lung disease of newborns.

This paper considers methods for estimating the relationship between a binary response Y and the genetic effects responsible for a second binary trait Z. The responses Y are observed only for target individuals, and the responses Z are observed only for the relatives of these targets. The analysis consists of two parts. The first part concerns the analysis of the family data Z and the second part estimates the relation between the genetic effects and Y. For the family data, a generalized linear mixed model with a logit link and Gaussian genetic (random) effects is used. Estimates of the variances of the genetic effects are obtained by using a pseudo-profile log-likelihood method. Estimation of the log likelihood involves averaging over n-dimensional normal distributions, which is done by importance sampling. The methods used in the second part are straightforward. The methods are applied to a data set containing chronic lung disease (CLDN) responses of newborns and asthma (AS), allergy (AL), chronic bronchitis (CB) and eczema (EC) responses observed for the relatives of these newborns. The clinical question is whether genetic effects of AS, AL, CB, and EC have an effect on the risk for CLDN. It can be concluded that for AS, AL, CB, and EC, the influence of genetic effects is significant. However, these genetic predispositions have no significant effect on CLDN.

Asthma↗

PubMed2002

Sample-size redetermination for repeated measures studies.

Clinical trialists recently have shown interest in two-stage procedures for updating the sample-size calculation at an interim point in a trial. Because many clinical trials involve repeated measures designs, it is desirable to have available practical two-stage procedures for such designs. Shih and Gould (1995, Statistics in Medicine 14, 2239-2248) discuss sample-size redetermination for repeated measures studies but under a highly simplified setup. We develop two-stage procedures under the general mixed linear model, allowing for dropouts and missed visits. We present a range of procedures and compare their Type I error and power by simulation. We find that, in general, the achieved power is brought considerably closer to the required level without inflating the Type I error rate. We also derive an inflation factor that ensures the power requirement is more closely met.

Analysis of Variance↗

PubMed2005

Seasonality in symptom severity influenced by temperature or grass pollen: results of a panel study in children with eczema.

Although seasonal variations are well known in many patients with eczema, no systematic population-based panel study evaluating seasonality and quantifying the influence of factors like climate and pollen on symptom variations has been conducted so far. Thirty-nine children with eczema, who had been identified in 1996 in a cross-sectional study on 1673 6-y-olds in Augsburg (Germany), participated in the study. Between March and September 1999, they daily recorded itch, extent, and possibly triggering factors on quantitative scales. Daily temperature, humidity, radiation, and pollen concentration were measured. Mixed linear models, taking the time series structure and confounding into account, were used for analysis. Seasonal patterns were significantly different between children: twenty-one had symptoms mainly in winter. They were affected by changes in outdoor temperature: itch was reduced by 22% (95% confidence interval (CI): 16%-27%) and extent by 65% (CI: 54%-72%) per 15 degrees C temperature increase. Eighteen children exhibited more symptoms in summer and especially during days with high grass-pollen exposure when itch was 16% higher (CI: 8%-24%) and extent 19% (CI: 2%-39%). This effect was stronger for children sensitized against pollen. Consideration of the individual type of eczema may help to arrange appropriate preventive and therapeutic measures.

Allergens↗

PubMed2000

The emergency department experience of chest pain patients and their intention to delay care seeking for acute myocardial infarction.

This study investigated how patients' emergency department experience was related to their intention to delay action in response to future symptoms of acute myocardial infarction. A sample of 426 persons admitted to the emergency department with a chief complaint of chest pain and released from the emergency department were contacted by telephone. Patients were queried about their affective response to the emergency department experience, their satisfaction with emergency department staff communication, their intention to delay prompt action for acute myocardial infarction symptoms in the future, the influence of others in the decision to seek care, and medical and demographic status. The results of a mixed model linear regression analysis showed that the less education patients had (p = 0.007), the less sure they felt that going to the emergency department had been "the right thing to do" (p = 0.004), and the greater the degree of embarrassment (p = 0.0001), the greater was the intention to delay action for future symptoms of acute myocardial infarction. The results also showed that those patients who were prompted by health professionals to go to the emergency department were less likely to report intentions to delay for future symptoms (p = 0.036). It is important that emergency department staff reassure chest pain patients who are sent home that they did the right thing by coming to the emergency department for their symptoms. Providers need to be particularly sensitive to feelings of embarrassment.

Chest Pain↗

PubMed2006

A placebo-controlled study of retinal blood flow changes by pentoxifylline and metabolites in humans.

AIM: To investigate the possible effects of pentoxifylline metabolites on retinal blood flow in humans. METHODS: A randomized, placebo-controlled, four-period cross-over study that was observer blinded and partly blinded for the eight participants. On one occasion a placebo was given as an intravenous (i.v.) infusion over 100 min. On the other three occasions pentoxifylline was administered as i.v. infusions over 100 min at a rate of 3 mg min(-1). Before two of the pentoxifylline infusions the subjects were pretreated with either ciprofloxacin or rifampicin. Retinal blood flow was measured by scanning laser doppler flowmetry (SLDF) in a selected area of the central temporal retina before, during and until 5 h after the end of infusion. Blood samples for concentration analyses of pentoxifyllin, R-M1, S-M1, M4 and M5 were taken serially and areas under the curves (AUCs) were calculated. Linear mixed models were used for the statistical analyses. RESULTS: Mean AUCs (ng h ml(-1)) were significantly increased for pentoxifylline (1964 vs. 1453) and S-M1 (5804 vs. 4227), but not R-M1 when pentoxifylline was co-administered with ciprofloxacin. The mean AUC for M5 was significantly reduced when subjects were pretreated with rifampicin (2041 vs. 3080). Pentoxifylline with and without pretreatment with rifampicin significantly increased retinal blood flow assessed as mean flow, pulsation (i.e. 1-systole/diastole), and diastolic flow (but not during systole), compared with placebo. The increases over placebo were more pronounced on diastolic flow, 9.7% (95% confidence interval 4.2, 15.5) than on mean flow, 4.6% (1.1, 8.3) after pentoxifylline administration. With pentoxifylline after rifampicin pretreatment the corresponding differences were 11.7% (5.8, 17.9) and 5.1% (1.4, 7.8) over placebo, respectively. After co-administration of pentoxifylline and ciprofloxacin we saw only a nonsignificant trend towards increased flow during diastole, but a significant decrease in pulsation. When AUCs for pentoxifylline and its metabolites were used as regressor variables to retinal mean flow we found that pentoxifylline, R-M1 and M5 had coefficients with a positive sign indicating that they enhanced the retinal blood flow. In contrast, S-M1 and M4 had coefficients with negative sign and thus appeared to decrease the blood flow in subjects treated with pentoxifylline. CONCLUSION: The R-M1 and M5 metabolites of pentoxifylline contributed significantly to the effects of pentoxifylline on retinal blood flow.

Adult↗