Development of a mitochondrial DNA real-time polymerase chain reaction assay for quality control of pathogen reduction with riboflavin and ultraviolet light.

BACKGROUND AND OBJECTIVES: Transfusion is associated with a risk of infection and alloimmunization. Pathogen reduction using riboflavin and UV light (Mirasol treatment) inactivates pathogens and leucocytes. With increasing adoption of the technology in clinical use, regulatory agencies have recommended the introduction of quality control measures to monitor pathogen reduction efficacy. We sought to develop a real-time PCR-based assay to document the impact of pathogen reduction on the mitochondrial genome in blood components. MATERIALS AND METHODS: DNA was extracted from platelet and plasma components before and after treatment with riboflavin and UV light. Inhibition of PCR amplification of mitochondrial DNA (mtDNA) in short- and long-amplicon target regions, ranging from under 200 base pairs (bp) to over 1800 bp, was measured in treated relative to untreated components. RESULTS: Pathogen reduction of platelets using riboflavin and UV light resulted in inhibition of PCR amplification of long-amplicon mtDNA targets, demonstrating approximately 1 log reduction of amplification relative to untreated products. Amplification of short-amplicon mtDNA targets was not affected by treatment. Evaluation of 110 blinded platelet samples from the PREPAReS clinical trial resulted in prediction of treatment status with 100% accuracy. Pathogen reduction of plasma components resulted in similar levels of PCR inhibition, while testing of 30 blinded plasma samples resulted in prediction of treatment status with 93% accuracy. CONCLUSION: A differential sized amplicon real-time PCR assay of mitochondrial DNA effectively documents nucleic acid damage induced by Mirasol treatment of platelets. The use of the assay for plasma product pathogen reduction requires further investigation.

Computer-automated dementia screening using a touch-tone telephone.

BACKGROUND: This study investigated the sensitivity and specificity of a computer-automated telephone system to evaluate cognitive impairment in elderly callers to identify signs of early dementia. METHODS: The Clinical Dementia Rating Scale was used to assess 155 subjects aged 56 to 93 years (n = 74, 27, 42, and 12, with a Clinical Dementia Rating Scale score of 0, 0.5, 1, and 2, respectively). These subjects performed a battery of tests administered by an interactive voice response system using standard Touch-Tone telephones. Seventy-four collateral informants also completed an interactive voice response version of the Symptoms of Dementia Screener. RESULTS: Sixteen cognitively impaired subjects were unable to complete the telephone call. Performances on 6 of 8 tasks were significantly influenced by Clinical Dementia Rating Scale status. The mean (SD) call length was 12 minutes 27 seconds (2 minutes 32 seconds). A subsample (n = 116) was analyzed using machine-learning methods, producing a scoring algorithm that combined performances across 4 tasks. Results indicated a potential sensitivity of 82.0% and specificity of 85.5%. The scoring model generalized to a validation subsample (n = 39), producing 85.0% sensitivity and 78.9% specificity. The kappa agreement between predicted and actual group membership was 0.64 (P<.001). Of the 16 subjects unable to complete the call, 11 provided sufficient information to permit us to classify them as impaired. Standard scoring of the interactive voice response-administered Symptoms of Dementia Screener (completed by informants) produced a screening sensitivity of 63.5% and 100% specificity. A lower criterion found a 90.4% sensitivity, without lowering specificity. CONCLUSIONS: Computer-automated telephone screening for early dementia using either informant or direct assessment is feasible. Such systems could provide wide-scale, cost-effective screening, education, and referral services to patients and caregivers.

Effectiveness of antidepressant pharmacotherapy: the impact of medication compliance and patient education.

This study was designed to investigate the impact of a time-phased patient education program (RHYTHMS) on medication compliance and treatment outcomes of primary care patients diagnosed with major depression and started on antidepressant pharmacotherapy. Two hundred forty-six depressed patients, diagnosed and treated at one of three outpatient clinics affiliated with the Kaiser-Permanente Northwest Region (KPNW) healthcare system, were randomly assigned to either receive or not receive (usual care) the educational materials by mail. Depression severity and functional impairment affecting patients' quality of life were assessed at baseline and 4, 12, and 30 weeks later. Self-reported impressions of improvement and patient satisfaction with treatment were also assessed at follow-up. Clinical assessment data were obtained using an interactive voice response (IVR) system. Study subjects were compensated $5, $10, $15, and $25 for completing each assessment (Baseline to Week 30, respectively). Upon study completion, prescription fill data of the subjects were extracted from the KPNW Pharmacy System for analysis of medication compliance. Most of the study subjects (63.5%) responded to the pharmacotherapy treatment by study end-point. Few statistically significant differences in either treatment outcomes or duration of medication compliance were found between the treatment groups, and significant differences found were of fairly small magnitude. Patients not receiving the educational materials initially exhibited a more positive response to treatment (Week 4), but this difference did not persist at later follow-ups and was associated with significantly higher relapse rates. A strong time-dose relationship was evident between the duration of the initial treatment episode and treatment outcomes at follow-up, but randomized treatment assignment did not influence the duration of initial medication compliance. Educational programs designed to encourage depressed patients to obtain adequate pharmacotherapy likely provide medical benefits. Such benefits appear to be relatively subtle and methodological differences between studies contribute to inconsistent conclusions concerning observed benefits. The intent of providing time-phased educational materials to patients is to maximize the relevance of such information by synchronizing it with typical recovery processes and issues. This study suggests that additional efforts at engaging patients earlier after the initiation of treatment might be of most benefit.

Meeting the need for public education about dementia.

Research continues to advance the knowledge of pathophysiology and development of effective methods for treating patients with Alzheimer disease and other dementias. Dissemination of information is likely to be slowest among the general population, who may be the first to recognize dementia symptoms but may also be reticent to discuss concerns because of fear, embarrassment, and/or inadequate knowledge. The feasibility of providing public education and access to dementia resources was studied using a toll-free interactive voice response (IVR) telephone system. Public interest in this service and willingness to use this technology were evaluated in a 1-month study conducted in a predominantly rural upper Midwest county (population of 102,565). One hundred ninety-three calls were received during November 1999, with an average length of 9 minutes and 29 seconds. One in six calls lasted 15 minutes or longer. One third of the calls were received outside typical business hours (8:00 AM to 6:00 PM). Concern for a parent or grandparent was the most frequent reason (50.6%) given for the call. Self-concern was indicated by 24.7% of the callers. Callers provided positive feedback. Such IVR technology may provide a cost-effective bridge to the "digital divide" existing among elderly, lower socioeconomic status, and rural populations underrepresented as computer and Internet users.

Comparison of interactive voice response and written self-administered patient surveys for clinical research.

This study compared the use of an interactive voice response (IVR) system with a written survey to collect data. Consecutive patients seen in an orthopedic clinic completed the Short Musculoskeletal Function Assessment (SMFA) by either IVR or written questionnaire and then were asked to complete the form again 3-7 days later using the opposite modality. Patient response rates were analyzed for differences between the self-administered IVR and written modes of administration. Three orthopedic clinics participated in the study. No significant differences between method of administration or individual differences in response per patient were found. Therefore, no significant differences in measurement are found when IVR is compared to the written SMFA.

Lay person-based screening for early detection of Alzheimer's disease: development and validation of an instrument.

Symptoms of cognitive impairment reported to telephone interviewers by caregivers of 272 patients were analyzed with respect to research diagnoses of dementia. All patients received neuropsychological evaluation for establishing the research diagnoses. A data mining program that used machine learning algorithms produced an optimized binary decision tree for differentiating patient groups according to all available information. The results of this analysis were used to help four dementia experts create a dementia screening instrument amenable to application and scoring by nonclinical personnel. The validity of the resulting instrument was then evaluated in an independent sample of 103 patients administered neuropsychological testing within the previous 60 days. The psychometric properties of the empirically derived scale and its performance for discriminating control from probable or possible Alzheimer's patients indicate strong potential for use as a dementia screener for the general population.

Computerized assessment of depression and anxiety over the telephone using interactive voice response.

We examined the reliability and validity of computer-administered versions of the Hamilton Depression (HAMD) and Hamilton Anxiety (HAMA) Rating Scales that were administered over the telephone using Interactive Voice Response (IVR). In two identical studies (HAMD: N = 113, HAMA: N = 74), both the IVR- and clinician-administered versions were administered in a counterbalanced order to a heterogeneous sample of subjects with psychiatric disorders and controls. Both the IVR HAMD and HAMA demonstrated adequate internal-consistency reliability (.90 and .93, respectively) and test-retest reliability (.74 and .97, respectively). The correlation between the IVR and clinician was high (HAMD = .96; HAMA = .65). The mean score difference between the IVR and clinician versions was less than one point for both the HAMD (.69 of a point) and HAMA (.60 of a point). It took subjects 12.23 minutes to complete the IVR HAMD, compared to 15.21 minutes for the clinician version; and 11.27 minutes for the IVR HAMA, compared to 15.33 minutes for the clinician (p < .001 for both comparisons). Subjects rated the clinician better in the areas of how much they liked being interviewed and how well they were able to describe their feelings. However, they were significantly more embarrassed with the clinician than with the IVR. Results support the psychometric properties of the IVR versions of the HAMD and HAMA scales. IVR technology presents new opportunities for expanding the utility of computerized clinical assessment.

Administration of the Hamilton Depression Rating Scale using interactive voice response technology.

We compared the reliability and equivalence of scores on the Hamilton rating scale for depression obtained by an interactive voice response (IVR) system and by human raters among 367 subjects 18 to 79 years old. Structured clinical interviews indicated that 93 of these subjects met the DSM-IV criteria for current major depression. We also examined short forms using the IVR data. The results obtained with the long (17-item) IVR interview correlated with those of the face-to-face interview, as did the results of the short (six- and eight-item) IVR interviews. In a random sample of 264 subjects, linear transformations of IVR results produced scores equivalent to clinical scores in the validation sample. We conclude that computerized assessment of the severity of depression by touch-tone telephone presents expanded opportunities for outcome research.

Individual differences in alcohol responsivity: physiological, psychomotor and subjective response domains.

OBJECTIVE: Psychometrically stable measures of individual differences in response to consuming alcohol were developed as part of an ongoing project investigating "high-tolerant" drinking drivers. The derived measures were correlated with diagnostic criteria of alcohol abuse and dependence, as well as drinking frequency, heavy drinking and tolerance estimations. METHOD: Male subjects (N = 94), 21 to 59 years old, participated in each of two identical alcohol consumption sessions (mean dose = 0.78 g/kg). Multiple response measures obtained before and after drinking (mean BAC = 78 mg/dl, descending) were used to compute postconsumption regression residuals that were factor analyzed. RESULTS: Factors reflecting psychomotor, subjective and physiological responsivity to alcohol were extracted. Confirmatory factor analyses indicated consistent psychomotor and physiological factor structures across the two testing sessions, but a bifurcation of the subjective measures. Test-retest correlations of the responsivity residuals indicated medium to moderately large effect sizes (mean = .32, range = .15-.51). Residuals summated within each response domain indicate moderate internal consistency (mean = .56, range = .45-.72) and higher reliabilities than single measure indices (range = .53-.59). Summated residuals within the response domains suggest diminished responsivity is associated with more severe alcohol-use diagnoses and were differentially predictive of self-reported drinking practices. CONCLUSIONS: Alcohol responsivity is multidimensional. Individual differences across different domains can be measured reliably and are associated with different patterns of alcohol use and abuse. Greater attention should be given to the specific domain of alcohol responsivity measures obtained in past and future research that relates individual differences to alcohol-related problems.

Informal and formal care for the elderly: decision determinants and their implications.

In this article, a model is developed of the determinants of elderly health care choice between the options of informal care (i.e., provided by family and friends) and formal care (i.e., care provided via the market). These determinants are: Expertise Capacity, Resource Capacity, Time Capacity, Economic Rewards, Psychic Rewards, Trust, and Control. This model is based on the theoretical work of Lusch, Brown, and Brunswick (1992) in the marketing literature and a variety of empirical findings in health care literature. The Lusch et al. (1992) framework models the general determinants of an entity's choice between fulfilling needs on their own (i.e., internal exchange or self-production) or going to the market to fulfill their needs (i.e., external exchange). The goal of this article is to develop understanding of formal care and informal care use decisions, and to create managerial recommendations based on a sound theoretical understanding of the issues.

Validation of daily self-reported alcohol consumption using interactive voice response (IVR) technology.

OBJECTIVE: This study assesses the validity of daily self-reported drinking data obtained using an automated touch-tone interactive voice response (IVR) system. METHOD: Subjects (N = 30) reported alcohol consumption daily for 28 days using the IVR system. Concurrently, breath and saliva samples were obtained each night for objective determination of blood alcohol concentrations (BACs). Partners living with the subjects provided collateral reports daily. Retrospective drinking records were obtained from both partners at the outset of the study and from the target subjects at the end of the study, using timeline follow-back procedures referencing the target subjects' drinking over the previous 28-day period. RESULTS: Subjects reported drinking on 55.2% of the 840 possible subject days, and positive BAC readings were obtained on 25.9% of these days. The overall correlation between self-report and measured BAC was .72. Within-subject correlations between daily IVR reports and measured BACs ranged from -.07 to .92, with a mean of .57. The correlations between self-reported drinking and the collateral reports ranged from .18 to 1.0, with a mean of .89. Correlations between the daily self-reports and the timeline follow-back records obtained at the end of the study ranged from -.22 to .96, with a mean of .51. CONCLUSIONS: IVR technology provides an innovative, user-friendly methodology for obtaining valid measures of daily alcohol consumption. The validity of these measures may be differentially highest for frequent, heavy drinkers, a group for whom traditional assessment methods often produce the most biased underestimates.

Cycles of alcohol dependence: frequency-domain analyses of daily drinking logs for matched alcohol-dependent and nondependent subjects.

OBJECTIVE: This study was undertaken to evaluate possible differences in the patterns of daily alcohol use, in terms of periodicity or rhythmicity of consumption, between alcohol-dependent and nondependent drinkers otherwise matched on the basis of quantity and frequency of alcohol use. METHOD: Frequency-domain time-series analysis was applied to daily drinking logs of six alcohol-dependent and six nondependent male subjects matched for consumption quantity and frequency who had participated in a larger 112-day study of alcohol consumption patterns using an innovative touch-tone telephone method of daily self-report. Spectral analysis partitioned variance in the drinking logs among statistically independent frequency cycles of relatively heavier and lighter drinking. The percentage of variance accounted for by fast (< 4 days), medium (7 +/- 3 days) and slow (> 10 days) cycle periods was compared for diagnostic group differences. RESULTS: Effective matching precluded consumption quantity, frequency or variability differences between the groups. Spectral analysis of the time-series data revealed group differences in the rhythmicity, or cyclical characteristics, of the drinking logs. The drinking logs of alcohol-dependent subjects exhibited more pronounced weekly cycles, whereas drinking logs of nondependent subjects fluctuated over longer periods. CONCLUSIONS: Temporal patterns of regular alcohol use may be an important behavioral variable influencing the seriousness of consequences associated with drinking, which may partly elucidate the relatively weak relationship between dependence symptomatology and consumption quantity-frequency.

Self-report of drinking using touch-tone telephone: extending the limits of reliable daily contact.

OBJECTIVE: Retrospective self-reports of alcohol consumption are ubiquitous in the alcohol research field. Time frames of these reports range from a week to a year or longer and are subject to several influences of bias that may have important clinical, epidemiological and methodological consequences. In order to specify drinking patterns more precisely, a study was conducted to monitor alcohol consumption on a daily basis. METHOD: Subjects (N = 51) responded for 112 days on an Interactive Voice Response system by entering their data daily using the touch-tone pad of their telephone. Each day, subjects answered 11 questions relating to drinking (including quantity) and to variables believed to affect consumption (e.g., stress level). RESULTS: The overall response rate was 93.0%. Subjects reported consuming at least one drink on 51.2% of all 5,151 reporting days (mean number of drinks reported = 4.6). Following completion of the study, subjects were also asked to recall consumption retrospectively using a standard quantity-frequency questionnaire. CONCLUSIONS: The present study demonstrated that: (1) data can be collected on a daily basis efficiently, and (2) traditional methods of data collection (e.g., quantity-frequency) result in a significant underreporting bias for heavier drinkers.

When alcohol and water don't mix: diving under the influence.

The impairing effects of alcohol on divers' abilities to perform shallow-water entry dives were investigated under controlled conditions. Each of 13 male recreational divers, 21 to 35 years old, performed three shallow-entry dives during each of seven diving sessions at various blood alcohol concentrations (BACs). The mean group BACs of Diving Sessions 1-7 were 0, 17, 40, 71, 100, 123 and 97 mg/dl, respectively. Diving performances were videotaped and rated on their relative risk of injury due to contact with the pool bottom if the depth had actually been 3.5 feet. The data indicate progressive and significant impairment of diving performance at BACs of 40 mg/dl (or 0.04 g/dl, or 0.04%) and higher. Corroborating evidence of alcohol impairment was obtained from administering Field Sobriety Tests following Sessions 1, 5, 6 and 7; almost all subjects failed the tests at the higher BAC sessions. An analysis of the self-ratings of diving performances indicated that the divers were not aware of either their degraded performance or the increased risk of injury resulting from diving after drinking.

The media/information richness model as prescription for some health care service ills.

Because consumers are demanding more and better information from their health care providers, improving effectiveness and efficiency of communications is one way that health care providers can gain a competitive edge. The authors propose that health care communication effectiveness and efficiency can be improved by using the Media/Information Richness Model (MIR) in planning service delivery systems.

A modeling analysis of young drivers' judgments of accident risk due to alcohol use and other driving conditions.

Male (60) and female (60) college students who were under the legal drinking age completed a personal driving experience questionnaire and judged the probability of an accident occurring in 100 driving scenarios, half involving an intoxicated male driver and half a sober male driver. The scenarios also varied in terms of the safety levels of five other driving factors. Mathematical models derived from the probability judgments permitted measurement of the influence of the various driving factors on perceived risk. The driving factors in order of their influence on the accident probability judgments were driver intoxication-nonintoxication, vehicle speed, road conditions, driver mood and driving experience, which did not significantly differ, and the driver's experience with alcohol use. Accident probability estimates of the alcohol scenarios increased as an additive function of the other driving factors, whereas increased risk of an accident in the no-alcohol scenarios was more dependent upon multiple unsafe factors. Female students judged the probability of an accident higher overall than did male students. Subject drinking classification (abstain-light, moderate or heavy) was not related to accident probability estimates.

Treatment cost and rehospitalization rate in schizophrenic outpatients with a history of substance abuse.

Retrospective self-report data from 60 chronic schizophrenic outpatients in a community support program (CSP) were used to study the relationship between a history of substance abuse and rate of psychiatric rehospitalization and outpatient treatment cost. The sample showed a significant overall reduction in days spent in a psychiatric hospital or jail and in outpatient treatment expenses during the first year in the CSP. Although subjects with recent symptoms of substance abuse (N = 27) showed consistently smaller reductions than subjects with no history of substance abuse (N = 17) or subjects with no recent substance abuse symptoms (N = 16), the only significant difference between the groups was in the total number of days spent in an institution. However, the findings suggest that treatment of patients with concurrent substance abuse and schizophrenia is disproportionately more costly than that of patients without dual diagnoses.