bluuebunny/crossref_metadata_2025 huggingface dataset:
The Economic Impact of Migraine: An Analysis of Direct and Indirect Costs
Authors: Edmeads John , Mackell Joan A.
Published: August 2002

Objective.—This study examined whether individuals with migraine incurred greater direct and indirect costs than a matched group free of migraines.

Methods.—Using population‐based survey data, we matched individuals with migraine (n = 1087) and a migraine‐free control group one‐to‐one for age, sex, employment status, and number of comorbidities. We assessed the prior six months' direct medical care in terms of self‐reported hospital days and emergency department and physician visits. Costs were computed by multiplying utilization by unit costs and summing across categories. Indirect costs were calculated based on the number of days missed from employment or household activities.

Results.—The sample was 80% female and had an average of 39 years and 0.4 comorbid conditions. Two‐thirds were employed. Migraineurs had higher direct medical costs over the prior six months ($522 versus $415, P = .039), primarily due to a greater frequency of physician and emergency department visits. The cost of lost productivity for the migraine group was also higher, by more than $200 (P = .014). The combined total for direct and indirect costs was $1,242 for migraineurs and $929 for the comparison group (P = .006). Additional analyses comparing those with moderate versus severe migraine demonstrated that more severe migraineurs had higher costs for lost productivity ($1,021 versus $251, P<.001) and higher costs when direct and indirect costs were combined ($1,656 versus $685, P<.001).

Conclusion.—Migraine is an expensive illness and two‐thirds of the financial burden is linked to indirect costs. Consequently, individuals with migraine, employers, and insurance companies all have an economic stake in reducing the migraine burden.
Usefulness and Safety of Shortened Head‐Up Tilt Testing Potentiated with Sublingual Glyceryl Trinitrate in Older Patients with Recurrent Unexplained Syncope
Authors: Del Rosso Attilio , Ungar Andrea , Bartoli Paolo , Cellai Tommaso , Mussi Chiara , Marchionni Niccolò , Masotti Giulio , Di Studio della sincope dell'anziano The Gruppo Italiano
Published: August 2002

OBJECTIVES: To evaluate the sensitivity and tolerability of shortened, glyceryl trinitrate (GTN)‐potentiated, head‐up tilt test (HUT) in patients older and younger than 65 with unexplained syncope and to compare the specificity of GTN‐potentiated HUT (GTN‐HUT) in older and younger controls.

DESIGN: Methodological study.

SETTING: Syncope units in secondary and tertiary hospitals.

PARTICIPANTS: Three hundred twenty‐four consecutive patients with unexplained syncope (100 aged ≥65 (mean age ± standard deviation 73 ± 6; 35 men) and 224 aged <65 (41 ± 15; 111 men)) and 64 controls (29 aged ≥65 (73 ± 6; 13 men) and 35 aged <65 (42 ± 13; 16 men)).

INTERVENTION: Patients and controls were tilted upright to 60° for 20 minutes. If syncope did not occur, sublingual GTN (400 μg) was administered and 60° HUT was continued for 15 minutes. Responses were classified as positive, negative, or exaggerated (slow decrease in blood pressure with a slight decrease in heart rate after GTN).

MEASUREMENTS: Electrocardiogram and arterial pressure were monitored continuously.

RESULTS: GTN‐HUT was positive in 60% and 66% (NS), negative in 29% and 33% (NS), and exaggerated in 11% and 1% (P < .001) of older and younger patients, respectively. In older and younger controls, the GTN‐HUT was negative in 70% and 86% and exaggerated in 28% and 9% of cases, respectively, (P < .05). The overall specificity (considering as negative also the exaggerated responses) was 97% in older and 94% in younger subjects. No patient or control experienced serious side effects.

CONCLUSION: The shortened GTN‐HUT provides satisfactory positivity rate and specificity in older patients. This test may be considered as a diagnostic tool in assessing recurrent unexplained syncope in older patients.
Falls and Fear of Falling: Which Comes First? A Longitudinal Prediction Model Suggests Strategies for Primary and Secondary Prevention
Authors: Friedman Susan M. , Munoz Beatriz , West Sheila K. , Rubin Gary S. , Fried Linda P.
Published: August 2002

OBJECTIVES: Previous cross‐sectional studies have shown a correlation between falls and fear of falling, but it is unclear which comes first. Our objectives were to determine the temporal relationship between falls and fear of falling, and to see whether these two outcomes share predictors.

DESIGN: A 20‐month, population‐based, prospective, observational study.

SETTING: Salisbury, Maryland. Each evaluation consisted of a home‐administered questionnaire, followed by a 4‐ to 5‐hour clinic evaluation.

PARTICIPANTS: The 2,212 participants in the Salisbury Eye Evaluation project who had baseline and 20‐month follow‐up clinic evaluations. At baseline, subjects were aged 65 to 84 and community dwelling and had a Mini‐Mental State Examination score of 18 or higher.

MEASUREMENTS: Demographics, visual function, comorbidities, neuropsychiatric status, medication use, and physical performance–based measures were assessed. Stepwise logistic regression analyses were performed to evaluate independent predictors of falls and fear of falling at the follow‐up evaluation, first predicting incident outcomes and then predicting fall or fear‐of‐falling status at 20 months with baseline falling and fear of falling as predictors.

RESULTS: Falls at baseline were an independent predictor of developing fear of falling 20 months later (odds ratio (OR) = 1.75; P < .0005), and fear of falling at baseline was a predictor of falling at 20 months (OR = 1.79; P < .0005). Women with a history of stroke were at risk of falls and fear of falling at follow‐up. In addition, Parkinson's disease, comorbidity, and white race predicted falls, whereas General Health Questionnaire score, age, and taking four or more medications predicted fear of falling.

CONCLUSION: Individuals who develop one of these outcomes are at risk for developing the other, with a resulting spiraling risk of falls, fear of falling, and functional decline. Because falls and fear of falling share predictors, individuals who are at a high risk of developing these endpoints can be identified.
The Effect of Medicated Chewing Gums on Oral Health in Frail Older People: A 1‐Year Clinical Trial
Authors: Simons Debra , Brailsford Susan R. , Kidd Edwina A. M. , Beighton David
Published: August 2002

OBJECTIVES: To determine the effects of a medicated chewing gum on the oral health of frail older people.

DESIGN: A controlled, double‐blind trial using three groups based on random allocation of residential homes.

SETTING: Sixteen residential homes in West Hertfordshire, England.

PARTICIPANTS: One hundred eleven dentate subjects aged 60 and older who completed the 12‐month study.

INTERVENTION: Subjects were assigned to a chlorhexidine acetate/xylitol gum (ACHX) group, a xylitol gum (X) group, or a no‐gum (N) group. Subjects in the gum groups chewed two pellets for 15 minutes twice daily for 12 months.

MEASUREMENTS: Primary outcome measures were salivary flow rate, denture debris score, prevalence of angular cheilitis, and denture stomatitis; secondary outcome measures were salivary levels of caries‐associated microorganisms. A single examiner, who was blinded to group allocation, made all measurements at baseline before gum usage and at subsequent examinations after 3, 6, 9, and 12 months. Separate analyses were performed for subjects with dentures.

RESULTS: Subjects in the three groups were similar in most of their baseline characteristics. The stimulated whole saliva flow rate ± standard deviation increased significantly for the ACHX (1.4 ± 0.7 mL/min) and X (1.6 ± 0.9 mL/min) groups (P < .01) over baseline (ACHX = 0.9 ± 0.6 mL/min, X = 0.8 ± 0.6 mL/min) and N group levels (0.6 ± 0.9 mL/min). The levels of mutans streptococci, lactobacilli, and yeasts significantly increased (P < .05) in the X and N groups. Denture debris status was significantly lower in the ACHX and X groups than at baseline or in the N group (P < .01). The reductions of 91% and 75% in denture stomatitis and angular cheilitis prevalence, respectively, that occurred in the ACHX group were significantly greater (P < .01) than the reductions in the X group (denture stomatitis 62%, angular cheilitis 43%). Prevalence of denture stomatitis and angular cheilitis were not significantly changed in the N group.

CONCLUSION: The use of a medicated chewing gum significantly improved oral health in older occupants of residential homes. Chewing gums should be considered as a potential adjunct to other oral hygiene procedures in older subjects.
Improving Patient Outcomes of Home Health Care: Findings from Two Demonstration Trials of Outcome‐Based Quality Improvement
Authors: Shaughnessy Peter W. , Hittle David F. , Crisler Kathryn S. , Powell Martha C. , Richard Angela A. , Kramer Andrew M. , Schlenker Robert E. , Steiner John F. , Donelan‐McCall Nancy S. , Beaudry James M. , Mulvey‐Lawlor Kendra L. , Engle Karen
Published: August 2002

OBJECTIVES: To evaluate effects on patient outcomes of Outcome‐Based Quality Improvement (OBQI), a continuous quality improvement methodology for home health care (HHC).

DESIGN: A quasi‐experimental design with prospective pre/post and study/control components within two multiyear demonstration trials (occurring from 1995 to 2000) in which 73 home health agencies implemented OBQI, receiving several annual cycles of outcome reports to evaluate and enhance patient outcomes.

SETTING: New York and 27 other states.

PARTICIPANTS: The study involved 157,548 predominantly older adult patients admitted over 3 years to 54 OBQI agencies from 27 states in the National Demonstration Trial, 105,917 patients admitted over 4 years to 19 OBQI agencies in the New York State Trial, and 248,621 patients admitted over 3 years to non‐OBQI control agencies in the 27 demonstration states.

INTERVENTION: As a clinical management and administrative intervention, OBQI involves collecting, encoding, and transmitting patient‐level health status data to a central source that provides each OBQI agency with a risk‐adjusted outcome report comparing the agency's patient outcomes with those from a reference population and with its own outcomes from the prior period. Target outcomes are selected and focused plans of action implemented to change care behaviors. Outcome changes are evaluated through the next report cycle.

MEASUREMENTS: Outcome measures include hospitalization rates and improvement and stabilization outcome rates in functional, physiological, emotional/behavioral, and cognitive health.

RESULTS: For the National and New York State Demonstration Trials, the risk‐adjusted relative rates of decline in hospitalization of 22% and 26%, respectively, for OBQI patients over the 3‐year and 4‐year demonstration periods were significant (P < .001) and unparalleled by considerably smaller rates of decline for the non‐OBQI patients in the 27 states. The risk‐adjusted rates of improvement in OBQI target outcome measures of health status averaged 5% to 7% per year in both demonstration trials and were significantly greater (P < .05) than analogous improvement rates for nontarget comparison outcomes, which averaged about 1% per year.

CONCLUSION: It is feasible to integrate the programmatic, data collection, data transmission, and outcome enhancement components of OBQI into the day‐to‐day operations of home health agencies. The aggregate findings and the agency‐level evidence available from site‐specific communications suggest that OBQI had a pervasive effect on outcome improvement for home health patients. OBQI appears to warrant expansion and refinement in HHC and experimentation in other healthcare settings.
Suboptimal Duration of Antidepressant Treatments in the Older Ambulatory Population of Quebec: Association with Selected Physician Characteristics
Authors: Moride Yola , Du Fort Guillaume Galbaud , Monette Johanne , Ducruet Thierry , Boivin Jean‐François , Nathalie Champoux MD , Crott Ralph
Published: August 2002

OBJECTIVES: To assess the association between selected physician characteristics and suboptimal duration of antidepressant use in the older outpatient population.

DESIGN: Follow‐up of patients who were prescribed an antidepressant treatment by a cohort of physicians in Quebec.

SETTING: Community‐based older outpatient population in Quebec.

PARTICIPANTS: Retrospective cohort of 1,301 general practitioners (GPs) and 236 psychiatrists followed from 1991 to 1997.

MEASUREMENTS: Treatment duration of less than 180 days in 1996/97.

RESULTS: Premature interruption of antidepressant treatment was very frequent (44.7%). GPs, physicians who practice in metropolitan or urban regions, and those who have a proportion of older patients in their practice of less than 50% show a higher rate of premature interruption. These associations could not be accounted for by the choice of products, dosage, or patient characteristics.

CONCLUSION: We have identified physician characteristics that are associated with suboptimal duration of antidepressant use and conclude that further interventions should target subgroups of physicians.
Cost‐Effectiveness of Preventive Occupational Therapy for Independent‐Living Older Adults
Authors: Hay Joel , LaBree Laurie , Luo Roger , Clark Florence , Carlson Mike , Mandel Deborah , Zemke Ruth , Jackson Jeanne , Azen Stanley P.
Published: August 2002

OBJECTIVES:To evaluate the cost‐effectiveness of a 9‐month preventive occupational therapy (OT) program in the Well‐Elderly Study: a randomized trial in independent‐living older adults that found significant health, function, and quality of life benefits attributable to preventive OT.

DESIGN:A randomized trial.

SETTING:Two government‐subsidized apartment complexes.

PARTICIPANTS:One hundred sixty‐three culturally diverse volunteers aged 60 and older.

INTERVENTION:An OT group, a social activity group (active control), and a nontreatment group (passive control).

MEASUREMENTS:Use of healthcare services was determined by telephone interview during and after the treatment phase. A conversion algorithm was applied to the RAND 36‐item Short Form Health Survey to derive a preference‐based health‐related quality of life index, quality‐adjusted life years (QALYs), and the incremental cost‐effectiveness ratio for preventive OT relative to the combined control group.

RESULTS:Costs for the 9‐month OT program averaged $548 per subject. Postintervention healthcare costs were lower for the OT group ($967) than for the active control group ($1,726), the passive control group ($3,334), or a combination of the control groups ($2,593). The quality of life index showed a 4.5% QALY differential (OT vs combined control),P< .001. The cost per QALY estimates for the OT group was $10,666 (95% confidence interval = $6,747–$25,430). For the passive and active control groups, the corresponding costs per QALY were $13,784 and $7,820, respectively.

CONCLUSION:In this study, preventive OT demonstrated cost‐effectiveness in conjunction with a trend toward decreased medical expenditures.
Effect of Statin (HMG‐Co‐A‐Reductase Inhibitor) Use on 1‐Year Mortality and Hospitalization Rates in Older Patients with Cardiovascular Disease Living in Nursing Homes
Authors: Eaton Charles B. , Lapane Kate L. , Murphy John B. , Hume Anne L.
Published: August 2002

OBJECTIVES: To quantify the effect of statins on 1‐year mortality, hospitalizations, and decline in physical function among patients with cardiovascular disease (CVD) aged 65 and older living in nursing homes.

DESIGN: Retrospective cohort study.

SETTING: All Medicare/Medicaid certified nursing homes (N = 1,492) in Maine, New York, Mississippi, and South Dakota.

PARTICIPANTS: We identified 51,559 older patients with CVD from a population database that merged sociodemographic data and functional, clinical, and drug treatments from more than 300,000 newly admitted nursing home residents from 1992 to 1997. Statin users (n = 1,313) were matched with nonusers (n = 1,313) in the same facilities.

MEASUREMENTS: All‐cause mortality, hospitalization, combined endpoint of mortality or hospitalization, and decline in physical function were determined at 1 year, and survival analysis was performed.

RESULTS: Prevalence of statin use in this frail older cohort with CVD was 2.6%. Statin use varied by age, gender, comorbid condition, medication use, and cognitive and physical function. One‐year mortality was 229/1,000 person‐years in the statin group and 404/1,000 person‐years in the nonusers, with an adjusted hazard rate ratio (HRR) of 0.69, 95% confidence interval (CI) = 0.58–0.81. The estimated number needed to treat was seven (95% CI = 5–13). This association with improved all‐cause mortality was evident for women and men and for age groups 75 to 84, and 85 and older.

CONCLUSION: Statin therapy is associated with improved clinical outcomes, including reduction in 1‐year all‐cause mortality, and the combined endpoint of death or hospitalization in a frail older population with CVD. Some caution should be taken in interpreting these results because potential bias from residual confounding could affect these results.
Otosclerosis and Stapedoplasty in Older Adults
Authors: Salvinelli Fabrizio , Casale Manuele , Trivelli Maurizio , Di Peco Valerio , Greco Fabio
Published: August 2002

OBJECTIVES: To evaluate the efficacy of stapedoplasty in patients aged 60 and older, based on audiometric data and a questionnaire about quality of life.

DESIGN: A retrospective (1994–2000) study.

SETTING: People living in southern and central Italy.

PARTICIPANTS: Sixty‐three patients: 32 consecutive patients aged 60 and older (group 1) and 31 consecutive patients younger than 60 (group 2).

MEASUREMENTS: In each patient, we evaluated the pre‐ and postoperative auditory thresholds. Each patient answered a questionnaire about postoperative quality of life.

RESULTS: When comparing the pre‐ and postoperative air conduction thresholds and air‐bone gap in the patients aged 60 and older, a statistically significant (P < .001) improvement at each frequency was observed. When elaborating the answers to the questionnaire about postoperative quality of life, we noticed that the older patients experienced a greater improvement.

CONCLUSION: The results show that stapedoplasty offers greater improvement in quality of life for selected adults aged 60 and older than for younger adults. The operation also appears to be as safe for adults aged 60 and older as for younger adults. Stapedoplasty provides subjects with satisfactory social hearing level (hearing capacity sufficient for normal social relations) and slows the progression of otosclerosis. Providing older patients with good auditory functionality improves their state of health, quality of life, and cognitive processes.
Is Low‐Dose Oral Cobalamin Enough to Normalize Cobalamin Function in Older People?
Authors: Angela Garcia MD , Alicia Paris‐Pombo MD , Evans Lisa , Day Andrew , Freedman Morris
Published: August 2002

OBJECTIVES: To investigate whether the use of low‐dose oral cobalamin (Cbl) supplements by older persons, as frequently found in multivitamin preparations, affects their Cbl serum concentrations and function, determined by measurements of the serum Cbl‐related metabolites methylmalonic acid (MMA), homocysteine (HCYS), and methylcitric acid (MCTR).

DESIGN: Cross‐sectional study.

SETTING: Community.

PARTICIPANTS: Two hundred forty‐two independent, active, community‐living, older adult volunteers recruited from community events and activities for seniors.

MEASUREMENTS: We systematically collected data on vitamin supplement intake, diet, medications, and medical and surgical history. Serum was obtained for Cbl, MMA, HCYS, and MCTR, and creatinine and hematological parameters.

RESULTS: Serum levels of Cbl were significantly higher in subjects on oral Cbl supplements (2–37.5 μg/day). Similarly, serum levels of the metabolites MMA, HCYS, and MCTR were also lower in subjects on Cbl supplementation. Intake of low‐dose oral supplements of Cbl significantly reduced the odds of low Cbl levels or high MMA. The relationship between Cbl supplement dosage and the biochemical parameters was dose dependent.

CONCLUSION: Oral Cbl (2–37.5 μg/day) intake by community‐dwelling healthy older adults is associated with higher serum levels of Cbl and improved or normalized Cbl function, as indicated by lower concentrations of the metabolites MMA, HCYS, and MCTR. Use of low‐dose oral Cbl replacement therapy might be sufficient to prevent Cbl deficiency in a large proportion of this population.
Common Chronic Diseases and General Impairments as Determinants of Walking Disability in the Oldest‐Old Population
Authors: Der Wiel Annetje Bootsma‐van , Gussekloo Jacobijn , De Craen Anton J.M. , Van Exel Eric , Bloem Bastiaan R. , Westendorp Rudi G.J.
Published: August 2002

OBJECTIVES: Walking disability affects older people's autonomy and well‐being. We investigated the relative effect of common chronic diseases and general impairments on walking disability in the general oldest‐old population.

DESIGN: Population‐based cohort study.

SETTING: Leiden 85‐plus Study, the Netherlands.

PARTICIPANTS: Five hundred ninety‐nine persons aged 85, response rate 87%.

MEASUREMENTS: Walking disability was assessed using a 6‐meter walking test. Persons with a walking time below the 25th percentile and those who were physically unable to perform the walking test were categorized as having a walking disability. Information on common chronic diseases was obtained from records of subjects' general practitioners and pharmacies. General impairments were assessed with functional tests and standardized questions during face‐to‐face interviews. We expressed the effect of common chronic diseases and general impairments as the population attributable risk (PAR), indicating how much disability can be prevented when the identified risk factor is eliminated from the population.

RESULTS: One hundred ninety‐two persons (33%) had a walking disability. This disability was highly associated with poor mobility in daily life, recurrent falls, and poor well‐being (all P < .001). Of the common chronic diseases, stroke, angina pectoris, diabetes mellitus, and hip fracture but not arthritis contributed most (PARs from 6% to 15%) to walking disability in the population at large. General impairments had higher prevalence rates and higher PARs than common chronic diseases. Cognitive impairment, depressive symptoms, and dizziness upon rising contributed most (PARs between 22 to 27%) to walking disability. In multivariate regression analyses of all common chronic diseases and general impairments, associations remained significant.

CONCLUSION: Within the general oldest‐old population, general impairments contribute more substantially to walking disability than do common chronic diseases. The diagnosed diseases did not explain the impairments that led to walking disability. Especially in the oldest old, clinicians should focus not merely on common chronic diseases but particularly on general impairments as targets for diagnostic analysis and treatment to decrease walking disability.
Factors Influencing the Use of Computer Technology in the Collection of Clinical Data in a Predominantly African‐American Population
Authors: Izquierdo‐Porrera Anna Maria , Manchanda Roopak , Powell Claudia C. , Sorkin John D. , Bradham Douglas D.
Published: August 2002

OBJECTIVES: To determine the cognitive and demographic factors that affect the performance of a predominantly African‐American population in the use of a computerized version of the Center for Epidemiologic Studies Depression Scale (CES‐D).

DESIGN: Cross‐sectional.

SETTING: University Medical Center and Veterans Affairs Medical Center in Baltimore, Maryland.

PARTICIPANTS: Forty‐three healthy community‐dwelling adults from a predominantly African‐American Apostolic church; mean age ± standard deviation 57 ± 14 (range 29–83).

MEASUREMENTS: Cognitive measurements (Mini‐Mental State Examination, digits span, word list learning, letter number sequencing, executive interview, and clock‐drawing task), education level, computer experience, and age. The CES‐D was administered on three occasions: a paper form CES‐D once and a computerized version twice. Time to completion the computer CES‐D (Time 1), differential in time to completion of both computer tests (delta‐time) and scores of the CES‐D with both forms of administration were recorded.

RESULTS: There was no difference between the scores from the paper and the computer CES‐D or between the two computer forms. Computer experience predicted Time 1 (partial correlation R = 15%, P = .017) and delta‐time (partial correlation R = 10%, P = .048). Age, education, and cognitive function did not affect performance.

CONCLUSION: Computerized assessment techniques are valid and unaffected by age, education level, or cognitive factors in healthy individuals.
Indicators of the Quality of Nursing Home Residential Care
Authors: Saliba Debra , Schnelle John F.
Published: August 2002

OBJECTIVES: To identify quality indicators (QIs) that can be used to measure nursing home (NH) residential care processes.

DESIGN: Modified‐delphi panel process to rate potential QIs that were identified through reported interviews with residents and families and through a review of the scientific literature.

SETTING: Meetings of panel of experts.

PARTICIPANTS: A national panel of nine experts in NH care rated potential QIs. A content expert and a clinical oversight committee performed external reviews.

MEASUREMENTS: Panelists' median validity and importance ratings for each QI choice.

RESULTS: The panel considered 64 choices for QI content and rated 28 of these as valid and important for measuring residential care quality. These 28 choices translated into 18 QIs. The external review process resulted in the addition of one QI that was not considered by the NH panel. The 19 indicators address areas identified as important by residents and proxies. Ten of these QIs were rated feasible to implement with current resources in average community NHs, and nine were rated feasible only in better NHs. The panelists identified nine as being measured most reliably by direct observations of care.

CONCLUSION: Experts identified 19 specific care processes as valid and important measures of the quality of NH residential care. Nine of these QIs may be measured best by direct observation of NH care, rather than by interviews or review of existing NH records. Almost half of the QIs were viewed as discriminating between better and average NHs. The panel deemed that only well‐staffed nursing homes could consistently implement nine of the QIs.
Mixed Dementia: Epidemiology, Diagnosis, and Treatment
Authors: Zekry Dina , Hauw Jean‐Jacques , Gold Gabriel
Published: August 2002

Alzheimer's disease (AD) and vascular dementia (VaD) are the most frequent causes of dementia in older people. Although AD can be diagnosed with a considerable degree of accuracy, the distinction between isolated AD, VaD, and mixed dementia (MD), where both pathologies coexist in the same patient, remains a controversial issue and one of the most difficult diagnostic challenges. Although MD represents a very frequent pathology, especially in older people, as reported in neuropathological studies, the respective importance of degenerative and vascular lesions, their interaction in the genesis of dementia, and the mere existence of MD are still debated. Accurate diagnosis of MD is of crucial significance for epidemiological purposes and for preventive and therapeutic strategies. Until recently, pharmacological studies have generally focused on pure disease, AD or VaD, and have provided little information on the best therapeutic approach to MD. This article provides an overview of MD in older people. A retrospective review of the recent literature on prevalence, incidence, course, risk factors, diagnosis, and treatment of MD was performed. The article also emphasizes the need for further studies, including neuropsychological and functional evaluations, and neuroimaging and clinicopathological correlations to develop a better understanding of MD, which appears to be one of the most common forms of dementia.
NAT for HBV and anti‐HBc testing increase blood safety
Authors: Roth W. Kurt , Weber Marijke , Petersen Detlev , Drosten Christian , Buhr Sylvia , Sireis Walid , Weichert Wolfgang , Hedges Doris , Seifried Erhard
Published: September 2002

BACKGROUND: Routine HBV PCR screening of blood donations to our institutes was introduced in January 1997 to complete the NAT screening program for transfusion‐relevant viruses. Testing was successively extended to customer transfusion services with a total of 1,300,000 samples tested per year.

STUDY DESIGN AND METHODS: Minipools of 96 blood donation samples were formed by automatic pipettors. HBsAg‐reactive samples were included. HBV particles were enriched from the minipools by centrifugation. Conventional and in‐house TaqMan PCRs were successively applied for HBV amplification. Sensitivity reached 1000 genome equivalents per mL for each individual donation. Confirmatory single‐sample and single‐sample enrichment PCRs were established with sensitivities of 300 and 5 to 10 genome equivalents per mL, respectively.

RESULTS: After screening of 3.6 million donor samples, 6 HBV PCR‐positive, HBsAg‐negative donations were identified. Two samples were from infected donors who had not seroconverted and four were from chronic anti‐HBc‐positive low‐level HBV carriers. Retesting by single‐sample PCR of 432 samples confirmed positive for HBsAg identified 37 donations that were negative in minipool PCR. Donor‐directed look‐back procedures indicated that no infected donor who had not yet seroconverted was missed by minipool PCR. However, recipient‐directed look‐back procedures revealed two anti‐HBc‐positive recipients of HBsAg‐negative minipool PCR‐negative, anti‐HBc‐positive and single‐sample PCR‐positive blood components. After testing randomly selected 729 HBsAg‐negative minipool PCR‐negative, anti‐HBc‐positive donors by single‐sample enrichment PCR, 7 were identified with ≤10 HBV particles per mL of donor plasma.

CONCLUSION: Minipool PCR testing after virus enrichment was sensitive enough to identify HBsAg‐negative donors who had seroconverterd and HBsAg‐negative, anti‐HBc‐positive chronic HBV carriers. HBV NAT in conjunction with anti‐HBc screening would reduce the residual risk of transfusion‐transmitted HBV infection.
Yield of HCV and HIV‐1 NAT after screening of 3.6 million blood donations in central Europe
Authors: Roth W. Kurt , Weber Marijke , Buhr Sylvia , Drosten Christian , Weichert Wolfgang , Sireis Walid , Hedges Doris , Seifried Erhard
Published: September 2002

BACKGROUND: HCV and HIV‐1 NAT of all blood donations was initiated at our institutions in January 1997 to reduce the residual risk of transfusion‐transmitted virus infections. The yield of NAT after testing more than 3.6 million donations in central Europe is reported.

STUDY DESIGN AND METHODS: Automated pipetting instruments were used to pool up to 96 donor samples including those that were antibody reactive. To compensate for dilution of the individual donor samples by pooling, viruses were enriched from the pools by centrifugation at 48,000 ×g. A commercial PCR (Cobas Amplicor, Roche) and an in‐house PCR were applied for HCV and HIV‐1 amplification, respectively.

RESULTS: Six HCV and 2 HIV‐1 PCR confirmed‐positive, antibody‐negative donations (yield, 1 in 600,000 and 1 in 1.8 million, respectively) were identified. Thirty‐nine and 11 multiple‐time donors seroconverted for HCV and HIV, respectively, and look‐back procedures were initiated. Archived samples from preseroconversion donations were thawed and retested by single‐sample PCR and remained negative. The recipients of the blood components were traced and tested. All traced recipients were negative for HCV and HIV antibodies.

CONCLUSION: The yield of NAT in central European Red Cross blood donors was less than expected from theoretical calculations for American and German multiple‐time donors. Look‐back procedures for HCV and HIV indicated that no donation given before seroconversion of the donor was missed by minipool PCR. Sensitivity of minipool PCR testing after virus enrichment seems to be sufficiently high to close the diagnostic window almost completely.
Change in CD34+ cell concentration during peripheral blood progenitor cell collection: effects on collection efficiency and efficacy
Authors: Ford Clyde D. , Greenwood Jay , Strupp Annie , Lehman Chris M.
Published: September 2002

BACKGROUND: An understanding of factors affecting CD34+ cell collection efficacy is essential to minimize donor toxicity and cost.

STUDY DESIGN AND METHODS: Peripheral blood CD34+ cell (CD34) measurements were determined at various intervals before, during, and after automated cell collection (Cobe Spectra 6.0). The serial mean of multiple, intraprocedural CD34 levels was calculated for each procedure as an estimate of the mean, inlet‐line CD34 level.

RESULTS: The CD34+ concentration fell a mean of 30 percent in the first 30 to 70 minutes of collection. The degree of decline was inversely correlated with donor blood volume (BV), but was not due to hemodilution. The mean of the CD34 level before and after collection slightly overestimated the serial mean CD34 level. Cell yields, normalized for the CD34 level before collection, were higher from donors with larger BVs.

CONCLUSIONS: The CD34 concentration rapidly decreased to a relative equilibrium level during the collection procedure. The degree of decrease in the CD34 level inversely correlated with the BV of the donor and was consistent with cell pooling in the collection set. The higher equilibrium CD34 levels in donors with larger BVs resulted in increased collection of CD34+ cells, and therefore, large‐volume apheresis should be most efficient in these donors.
Equivalent mobilization and collection of granulocytes for transfusion after administration of glycosylated G–CSF (3 μg/kg) plus dexamethasone versus glycosylated G–CSF (12 μg/kg) alone
Authors: Heuft H.G. , Goudeva L. , Sel S. , Blasczyk R.
Published: September 2002

BACKGROUND: The aim of this study was to find a regimen for mobilization and collection of granulocytes that combines low‐dose G–CSF administration with satisfactory PMN mobilization and apheresis at a low rate of donor adverse reactions.

STUDY DESIGN AND METHODS: In a prospective study, 52 healthy unrelated volunteers received a single subcutaneous injection of glycosylated G–CSF (Lenograstim Chugai‐Pharma, Frankfurt, Germany) at medians of 3.1 (range, 2.4‐3.6) μg per kg plus dexamethasone (8 mg orally; n = 29) or at 11.8 (7.1‐18.5) μg of lenograstim per kg (p ≤ 0.0001) without dexamethasone (n = 23) and underwent standard apheresis using the PMN program of a cell separator (Spectra, COBE [now Gambro] BCT). WBC and PMN mobilization results and apheresis yields were compared and the severity and clinical significance of donor adverse reactions was evaluated.

RESULTS: For the low‐dose G–CSF plus dexamethasone versus the high‐dose G–CSF alone group, similar mobilization results were observed for WBCs with 31.3 (19.1‐44.9) × 109 per L versus 27.5 (19.2‐44.0) × 109 per L (p = 0.21, NS) and PMNs with 29.0 (17.6‐42.2) × 109 per L versus 25.2 (16.2‐39.0) × 109 per L (p = 0.08, NS). The PMN apheresis yields were equal with 70 (39‐139) × 109 per unit with low‐dose G–CSF versus 68 (33‐120) × 109 per unit in the high‐dose G–CSF group (p = 0.83, NS). Regarding donor adverse reactions, 7 out of 29 (24%) and 8 out of 23 donors (35%) reported moderate or severe symptoms. The character of these reactions was different; symptoms of greater clinical significance and a higher need for analgesics were observed in the high‐dose G–CSF group.

CONCLUSIONS: A Lenograstim dose of 3 μg per kg plus DXM assures effective PMN mobilization and acceptable apheresis components. The combination of glycosylated G–CSF with DXM allows a significant dose reduction in G–CSF for PMN mobilization and collection as compared with higher G–CSF doses alone. In the high‐dose G–CSF mobilization group, adverse reactions were more severe and required more analgesics.
Experience with universal bacterial culturing to detect contamination of apheresis platelet units in a hospital transfusion service
Authors: AuBuchon James P. , Cooper Linda K. , Leach Miriam F. , Zuaro Deborah E. , Schwartzman Joseph D.
Published: September 2002

BACKGROUND: Bacterial contamination of platelet units poses one of the greatest risks of morbidity and mortality to platelet transfusion recipients. A routine culture of all units (WBC‐reduced apheresis platelet units) was instituted on Day 2 over a 2‐year period to reduce this risk.

STUDY DESIGN AND METHODS: A sterile connecting device was used to attach a small transfer pack on the morning of Day 2 after collection, and 10 mL of the unit were transferred to the small bag. After disconnection from the unit, about half of this volume was transferred to an aerobic culture bottle of an automated bacterial detection system. Units were maintained in available inventory until and unless a report was received of growth in the sample. When available, the unit or a retained aliquot was recultured if the initial sample was positive. Units were held up to 2 days beyond their 5‐day outdate and used for transfusion if no other suitable units were available to meet the clinical need or were evaluated with in vitro testing on Day 8.

RESULTS: Of 2678 units cultured, 16 (0.6%) were positive on initial culture. Thirteen could be recultured, and all of these samples were negative. Shortly after the 2‐year period of the study, two units (split from the same collection) were documented as growing coagulase‐negative Staphylococci 12 hours after sampling. Units transfused on Day 6 or 7 (n = 40) yielded expected clinical responses, and CCI available on 21 recipients 10 to 60 minutes after transfusion demonstrated acceptable results (mean, 14,400 ± 8800; median, 12,191; 90% > 7500). More than 96 percent of units tested on Day 8 had pH greater than 6.2 and continued to demonstrate swirling.

CONCLUSIONS: Routine culturing of apheresis platelet units is feasible, can be accomplished with a low rate of false positivity, and can detect contaminated units. The cost of such a protocol could be mitigated with extension of the storage period, and clinical experience with units held for 6 or 7 days was satisfactory.
Quantification of fetomaternal hemorrhage by fluorescence microscopy is equivalent to flow cytometry
Authors: Ochsenbein‐Imhof Nadin , Ochsenbein A.F. , Seifert B. , Huch Albert , Huch Renate , Zimmermann Roland
Published: September 2002

BACKGROUND: The quantification of fetal cells in the maternal circulation remains an important goal to determine the amount of anti‐D necessary to prevent active immunization of a D– mother giving birth to a D+ baby. Underestimation of fetomaternal hemorrhage (FMH) results in inefficient anti‐D prophylaxis and maternal immunization; overestimation of FMH results in higher doses of passively transferred anti‐D, higher costs, and the risk of disease transmission. Thus, a reliable method to quantitatively assess FMH is necessary.

STUDY DESIGN AND METHODS: Serial dilutions of artificial FMH were quantitatively measured by three different methods: flow cytometry, fluorescence microscopy (each after anti‐D staining), and by the Kleihauer‐Betke test. The accuracy and precision of the three methods were compared by statistical analysis.

RESULTS: Fluorescence microscopy and flow cy‐ tometry were comparably accurate and precise in quantifying FMH. In contrast, the accuracy of the Kleihauer‐Betke test was poor, resulting in substan‐ tial overestimation of FMH in the samples with lower fetal cell concentrations.

CONCLUSION: Anti‐D flow cytometry and fluorescence microscopy for detection of fetal cells offer equally reliable and precise methods in contrast to the Kleihauer‐Betke test. Fluorescence microscopy may be established as standard to quantify FMH in clinical practice because it is comparable to flow cytometry; in addition, it is time saving and is less expensive.
Combined isolation of CD34+ progenitor cells and reduction of B cells from peripheral blood by use of immunomagnetic methods
Authors: Martín‐Henao G.A. , Picón M. , Rueda F. , Amill B. , Querol S. , Gonzalez‐Barca E. , Ferrá C. , Grañena A. , García J.
Published: September 2002

BACKGROUND: Malignant cells may contribute to relapse after autologous hematopoietic cell transplantation The effectiveness of a double immunomagnetic purging strategy combining CD34‐positive with B‐negative cell selection to purge peripheral blood progenitor cells (PBPCs) from patients with chronic lymphoproliferative disorders has been analyzed.

STUDY DESIGN AND METHODS: Twenty‐two CD34+ cell selections from patients with follicular lymphoma (n = 14), chronic lymphocytic leukemia (n = 6), mantle cell lymphoma (n = 1), and splenic marginal zone lymphoma (n = 1) were performed by use of a magnetic cell selector followed by a negative cell selection step with anti‐CD19 monoclonal antibody bound to immunomagnetic beads.

RESULTS: The PBPC components contained median CD34+ cells of 1.24 percent (range, 0.38‐3.92%) and CD19+ cells of 1.83 percent (range, 0.06‐69.7%). After positive selection (n = 22), 49 percent (range, 16‐72%) of CD34+ cells were recovered with a purity of 93 percent (range, 24‐99%). The double‐positive and ‐negative selections (n = 20) yielded 57.5 percent of CD34+ cells (range, 33.4‐79.4%) with a purity of 95 percent (range, 63‐99%). Logarithms of B‐cell reduction in the CD34+‐cell‐enriched B‐cell‐depleted component had a median value of 3.63 (range, 2.74‐4.84 log) and CD19+ and CD5+ cells for chronic lymphocytic leukemia patients with more than 4.56 log (>3.6‐5.6 log). Of 13 PBPC components that had a tumor‐specific clonal signal, 10 became PCR negative after the double‐selection procedure.

CONCLUSION: Combined positive and negative magnetic cell selection achieves a high grade of tumor cell reduction with up to 77 percent of the grafts being negative for tumor‐specific clonal signal by PCR analysis. This technique preserves an adequate recovery of progenitor cells able to engraft.
TT virus infection during childhood
Authors: Ohto Hitoshi , Ujiie Niro , Takeuchi Chikako , Sato Akira , Hayashi Akio , Ishiko Hiroaki , Nishizawa Tsutomu , For The Vertical Transmission of Hepatitis Viruses Collabora Hiroaki Okamoto
Published: September 2002

BACKGROUND: TT virus (TTV) is widespread in the general population, however, the mode of its transmission and the mechanism of maintaining it in the general population are unclear.

STUDY DESIGN AND METHODS: To determine the possible mother‐to‐infant route of transmission, 54 infants born to 50 anti‐HCV‐positive mothers were assessed longitudinally. Nucleotide sequences amplified by seminested PCR with primers targeting the N22 variable coding region of genotypes 1 through 6 were compared in mothers and their infants.

RESULTS: The prevalence of TTV DNA was 30 percent (15/50; 95% CI, 18‐45) in mothers and 44 percent (24/54; 95% CI, 31‐59) in their infants. TTV DNA was detected during a follow‐up period in 13 (87%; 95% CI, 60–98) of 15 infants born to infected mothers and in 11 (28%; 95% CI, 15‐45) of 39 infants born to DNA‐negative mothers. None of 38 cord blood samples, but one of 14 blood samples, obtained at 1 month of age had detectable TTV DNA. The lowest infection rate at the earliest ages and the subsequent increasing prevalence of infection (22% at 6 months and 33%[43% cumulative rate] at 2 years) is consistent with an age‐dependent acquisition of TTV by nonparenteral routes. In 13–mother‐infant pairs positive for TTV DNA, six showed a high degree of nucleotide sequence similarity (99.1‐100%), whereas the remaining seven pairs differed more than 10 percent from each other (46.8‐89.2%). The viral load of maternal blood was not a plausible risk factor for transmission. Genotype 1, of which pathogenicity failed to be shown by measurement of hepatic enzymes, was more rapidly cleared (88 vs. 8% other genotypes, p < 0.001) among infants.

CONCLUSIONS: These observations strongly suggest that the main factor for TTV acquisition in children involves their age‐associated increase in environmental interactions with infectious materials. Genotype 1 might be involved in a weak or a limited pathologic role, which can possibly be diluted by other harmless genotypes.
Controlled study of citrate effects and response to IV calcium administration during allogeneic peripheral blood progenitor cell donation
Authors: Bolan Charles D. , Cecco Stacey A. , Wesley Robert A. , Horne McDonald , Yau Yu Ying , Remaley Alan T. , Childs Richard W. , Barrett A. John , Rehak Nadja N. , Leitman Susan F.
Published: September 2002

BACKGROUND: Leukapheresis procedures are generally performed at citrate anticoagulation rates extrapolated from shorter plateletpheresis procedures. However, neither the metabolic effects nor the management of associated symptoms have been critically evaluated during leukapheresis in healthy donors.

STUDY DESIGN AND METHODS: Symptom assessments (n = 315) and laboratory analyses (n = 49) were performed during 244 procedures performed with and 71 without prophylactic calcium (Ca) chloride or Ca gluconate given at a dose linked to the citrate infusion rate (1.0‐2.2 mg/kg/min).

RESULTS: During leukapheresis of 12 to 25 L processed, ionized Ca and ionized magnesium (Mg) decreased as much as 35 and 56 percent, respectively, each exhibiting a tight negative correlation with marked increases in serum citrate levels. Significant increases in urinary Ca and Mg excretion accompanied the renal excretion of a large citrate load. Serum divalent cation levels remained depressed 24 hours after leukapheresis. Symptoms were more frequent in donors who were women, had low initial total Mg levels, and underwent procedures in which larger volumes were processed at higher citrate infusion rates. Ca infusions reduced clinically significant paresthesias by 96 percent and also attenuated decreases in serum potassium. Ca chloride maintained higher Ca levels than Ca gluconate.

CONCLUSIONS: Prophylactic Ca infusions safely attenuate the marked metabolic effects of citrate administration and promote faster, more comfortable, leukapheresis procedures.
Dielectric behavior and diffuse phase transition features of rare earth doped Sr0.61Ba0.39Nb2O6 ferroelectric ceramics
Authors: Santos I. A. , Spı́nola D. U. , Garcia D. , Eiras J. A.
Published: August 2002

The dielectric behavior and the main features of the diffuse phase transition of nondoped and rare earth (La, Nd, or Gd) doped Sr0.61Ba0.39Nb2O6 relaxor ferroelectric ceramics were carefully investigated. The dopant incorporation gives rise to one continuous decrease of the temperatures of maximum dielectric permittivity. The whole set of the effects of rare earth (RE) doping on SBN diffuse phase transition and relaxation features can be attributed to the RE site distribution. In fact, the dopant incorporates into the tungsten bronze A2 sites, giving rise to the strong random field sources that act mainly on destroying the ferroelectric long-range interactions. This A2-sites occupation also affects the dielectric permittivity frequency response, whereas the relaxation strength (ΔTrs=Tm(1 MHz)−Tm(100 Hz)) increases with RE content increasing. This effect can be explained considering that the dopant roughens the free energy landscape, promoting strong changes in the volume size distribution of the interacting ferroelectric clusters.