A low cost, re-usable electricity-free infant warmer: evaluation of safety, effectiveness and feasibiliy.

Setting: Rural Rwandan hospitals, where thermoregulation is critical yet a challenge for pre-term, low-birth-weight (LBW) or sick newborns. Objective: To assess the safety, effectiveness, and feasibility of an inexpensive, reusable, non-electric warmer to complement kangaroo mother care (KMC). Methods: Prospective single-arm, non-randomized intervention study. Enrolled infants were hypothermic or at risk of hypothermia due to prematurity/LBW. Infants used the warmer in conjunction with KMC or as the sole source of external heat. Temperatures of the infant, warmer and air were measured for up to 6 h. Results: Overall, 33 patients used the warmer for 102 encounters: 43 hypothermic and 59 at risk of hypothermia. In 7/102 encounters (7%), the infant developed a temperature of >37.5°C (37.6°-38.2°C). For 43 hypothermic encounters and 59 at-risk encounters, hypothermia was corrected/prevented in respectively 41 (95%) and 59 (100%) instances. The warmer maintained goal temperature for the study duration in ⩾85% of uses. Two/12 warmers broke down after <10 uses. In no instances was the warmer used incorrectly. Conclusion: Our results are promising for this prototype design, and warrant testing on a wider scale.

Contexte : Des hôpitaux ruraux du Rwanda où la thermorégulation est cruciale mais complexe pour les nouveaux-nés prématurés, de faible poids de naissance (LBW) ou malades.Objectif : Evaluer la sécurité, l'efficacité et la faisabilité d'un réchauffeur peu coûteux, réutilisable et non électrique pour compléter la méthode kangourou (KMC).Méthode : Etude rétrospective d'intervention à un seul bras, non randomisée. Les nouveaux-nés enrôlés étaient en hypothermie ou à risque d'hypothermie liée à la prématurité ou au LBW. Les nouveaux-nés ont bénéficié du réchauffeur en conjonction avec la méthode KMC ou comme source unique de chaleur externe. Les températures des bébés, du réchauffeur et de l'air ont été mesurées pendant 6 h.Résultats : Ont bénéficié du réchauffeur 33 patients pour un total de 102 utilisations ; 43 étaient en hypothermie et 59 à risque d'hypothermie. Dans 7/102 utilisations (7%), le bébé a atteint une température de >37,5°C (37,6°­38,2°C). Dans 43 cas d'hypothermie et 59 cas à risque, l'hypothermie a été corrigée/prévenue dans 41 (95%) et 59 (100%) instances, respectivement. Le réchauffeur a maintenu la température souhaitée pendant la durée de l'étude dans ≥85% des utilisations. Deux réchauffeurs sur 12 ont été hors d'usage après moins de 10 utilisations. Il n'y a jamais eu d'utilisation incorrecte.Conclusion : Nos résultats sont prometteurs en ce qui concerne la conception de ce prototype et ils justifient une évaluation à plus grande échelle.

Marco de Referencia: En varios hospitales rurales de Rwanda, la termorregulación que es fundamental para los recién nacidos con bajo peso al nacer o enfermos, plantea dificultades.Objetivo: Evaluar la seguridad, la eficacia y la factibilidad de un dispositivo no eléctrico, de bajo costo y reutilizable que genera calor como complemento al método de la madre canguro (KMC).Métodos: Fue este un estudio prospectivo de intervención con un solo grupo, no aleatorizado. Se incluyeron lactantes que ya sea, estaban hipotérmicos o expuestos a la hipotermia debido a su prematuridad o el bajo peso al nacer. Con estos lactantes, se utilizó el calentador como fuente externa exclusiva de calor o en asociación con el KMC. Se midieron las temperaturas del lactante, el calentador y la temperatura ambiente durante un máximo de 6 h.Resultados: Se utilizó el dispositivo en 102 encuentros con 33 pacientes, de los cuales 43 estaban hipotérmicos y 59 estaban en riesgo de entrar en hipotermia. En siete de los 102 encuentros (7%), el lactante alcanzó una temperatura superior a 37,5°C (37,6°­38,2°C). La hipotermia se corrigió en 41 de los 43 encuentros con lactantes hipotérmicos (95%) y se evitó en 59 de las 59 ocasiones con bebés expuestos (100%). El calentador mantuvo la temperatura buscada durante todo el estudio en ≥85% de los encuentros en los cuales se utilizó. Dos de los 12 dispositivos exhibieron degradación después de menos de 10 utilizaciones. En ningún caso se utilizó el calentador de manera incorrecta.Conclusión: Los resultados obtenidos con este método prototipo son promisorios y se justifica realizar un ensayo clínico de mayor escala.

Mortality and cardiovascular disease among older live kidney donors.

Over the past two decades, live kidney donation by older individuals (≥55 years) has become more common. Given the strong associations of older age with cardiovascular disease (CVD), nephrectomy could make older donors vulnerable to death and cardiovascular events. We performed a cohort study among older live kidney donors who were matched to healthy older individuals in the Health and Retirement Study. The primary outcome was mortality ascertained through national death registries. Secondary outcomes ascertained among pairs with Medicare coverage included death or CVD ascertained through Medicare claims data. During the period from 1996 to 2006, there were 5717 older donors in the United States. We matched 3368 donors 1:1 to older healthy nondonors. Among donors and matched pairs, the mean age was 59 years; 41% were male and 7% were black race. In median follow-up of 7.8 years, mortality was not different between donors and matched pairs (p = 0.21). Among donors with Medicare, the combined outcome of death/CVD (p = 0.70) was also not different between donors and nondonors. In summary, carefully selected older kidney donors do not face a higher risk of death or CVD. These findings should be provided to older individuals considering live kidney donation.

Clinical trials and late-stage drug development for Alzheimer's disease: an appraisal from 1984 to 2014.

The modern era of drug development for Alzheimer's disease began with the proposal of the cholinergic hypothesis of memory impairment and the 1984 research criteria for Alzheimer's disease. Since then, despite the evaluation of numerous potential treatments in clinical trials, only four cholinesterase inhibitors and memantine have shown sufficient safety and efficacy to allow marketing approval at an international level. Although this is probably because the other drugs tested were ineffective, inadequate clinical development methods have also been blamed for the failures. Here, we review the development of treatments for Alzheimer's disease during the past 30 years, considering the drugs, potential targets, late-stage clinical trials, development methods, emerging use of biomarkers and evolution of regulatory considerations in order to summarize advances and anticipate future developments. We have considered late-stage Alzheimer's disease drug development from 1984 to 2013, including individual clinical trials, systematic and qualitative reviews, meta-analyses, methods, commentaries, position papers and guidelines. We then review the evolution of drugs in late clinical development, methods, biomarkers and regulatory issues. Although a range of small molecules and biological products against many targets have been investigated in clinical trials, the predominant drug targets have been the cholinergic system and the amyloid cascade. Trial methods have evolved incrementally: inclusion criteria have largely remained focused on mild-to-moderate Alzheimer's disease criteria, recently extending to early or prodromal Alzheimer disease or 'mild cognitive impairment due to Alzheimer's disease', for drugs considered to be disease modifying. The duration of trials has remained at 6-12 months for drugs intended to improve symptoms; 18- to 24-month trials have been established for drugs expected to attenuate clinical course. Cognitive performance, activities of daily living, global change and severity ratings have persisted as the primary clinically relevant outcomes. Regulatory guidance and oversight have evolved to allow for enrichment of early-stage Alzheimer's disease trial samples using biomarkers and phase-specific outcomes. In conclusion, validated drug targets for Alzheimer's disease remain to be developed. Only drugs that affect an aspect of cholinergic function have shown consistent, but modest, clinical effects in late-phase trials. There is opportunity for substantial improvements in drug discovery and clinical development methods.

Attenuation of resting energy expenditure following hematopoietic SCT in children.

Children undergoing hematopoietic SCT (HSCT) typically receive parenteral nutrition (PN) due to gastrointestinal toxicities. Accurate determination of resting energy expenditure (REE) may facilitate optimal energy provision and help avoid unintended overfeeding or underfeeding. A multicenter, prospective cohort study of children undergoing allogeneic HSCT was performed, in which REE was measured by indirect calorimetry at baseline and twice weekly until 30 days after transplantation. Change in percent predicted REE over time from admission was analyzed using repeated measures regression analysis. In all, 26 children (14 females) with a mean (s.d.) age of 14.9 (4.2) years who underwent an HLA-matched sibling or unrelated donor transplantation were enrolled. Mean (s.d.) percent predicted REE at baseline was 92.4 (15.2). Baseline REE was highly correlated with lean body mass measured by dual energy X-ray absorptiometry (r=0.78, P<0.0001). REE decreased significantly over time, following a quadratic curve to a nadir of 79% predicted at 14 days post transplantation (P<0.001) and returned to near baseline by day 30. Children undergoing HSCT exhibit a significant reduction in REE in the early weeks after transplantation, a phenomenon that places them at risk for overfeeding. Serial measurements of REE or reductions in energy intake should be considered when PN is the primary mode of nutrition.

Report of the task force on designing clinical trials in early (predementia) AD.

BACKGROUND: A large number of promising candidate disease-modifying treatments for Alzheimer disease (AD) continue to advance into phase II and phase III testing. However, most completed trials have failed to demonstrate efficacy, and there is growing concern that methodologic difficulties may contribute to these clinical trial failures. The optimal time to intervene with such treatments is probably in the years prior to the onset of dementia, before the neuropathology has progressed to the advanced stage corresponding to clinical dementia. METHOD: An international task force of individuals from academia, industry, nonprofit foundations, and regulatory agencies was convened to discuss optimal trial design in early (predementia) AD. RESULTS: General consensus was reached on key principles involving the scope of the AD diagnosis, the selection of subjects for trials, outcome measures, and analytical methods. CONCLUSION: A consensus has been achieved in support of the testing of candidate treatments in the early (predementia) AD population.

Assessment of differences in HLA-A, -B, and -DRB1 allele mismatches among African-American and non-African-American recipients of deceased kidney transplants.

Among recipients of deceased donor kidney transplants, African-Americans experience a more rapid rate of kidney allograft loss than non-African-Americans. The purpose of this study was to characterize and quantify the HLA-A, -B, and -DRB1 allele mismatches and amino acid substitutions at antigen recognition sites among African-American and non-African-American recipients of deceased donor kidney transplants matched at the antigen level. In recipients with zero HLA antigen mismatches, the degree of one or two HLA allele mismatches for both racial groups combined was 47%, 29%, and 11% at HLA-DRB1, HLA-B, and HLA-A, respectively. There was a greater number of allele mismatches in African-Americans than non-African-Americans at HLA-A (P < .0001), -B (P = .096), and -DRB1 loci (P < .0001). For both racial groups, the HLA allele mismatches were predominantly at A2 for HLA-A; B35 and B44 for HLA-B; but multiple specificities for HLA-DRB1. The observed amino acid mismatches were concentrated at a few functional positions in the antigen binding site of HLA-A and -B and -DRB1 molecules. Future studies are ongoing to assess the impact of these HLA mismatches on kidney allograft loss.

Economic evaluation of donepezil in moderate to severe Alzheimer disease.

OBJECTIVE: To investigate the costs to society of Alzheimer disease (AD) care in a multinational, randomized, placebo-controlled trial of donepezil in patients with moderate to severe AD. METHODS: A total of 290 patients with AD (screening standardized Mini-Mental State Examination score 5 to 17) were randomized to receive either donepezil (n = 144; 5 mg/day for 28 days, followed by 10 mg/day as per clinician's judgment) or placebo (n = 146) for 24 weeks. The authors collected data on patient and caregiver health resource utilization prospectively using the Canadian Utilization of Services Tracking questionnaire. Costs were calculated for patients and caregivers in each group based on resource utilization multiplied by the unit prices for each resource. A cost (the average Ontario minimum wage for 1998 [Can 6.85 dollars per hour]) was assigned to unpaid time that caregivers spent assisting the patient with activities of daily living (ADL). RESULTS: Patient and caregiver demographics at baseline were similar across the two groups. After adjusting for baseline total cost per patient, the mean total societal cost per patient for the 24-week period was donepezil, Can 9,904 dollars (US 6,686 dollars) and placebo, Can 10,236 dollars (US 6,910 dollars). This net cost saving of Can 332 dollars (US 224 dollars) included the average 24-week cost of donepezil treatment. Most of the cost-saving with donepezil treatment was due to less use of residential care by patients, and caregivers spending less time assisting patients with ADL. CONCLUSION: This cost-consequence analysis reveals economic benefits of treatment of moderate to severe AD with donepezil.

Possible effect of DRGs on the classification of stroke: implications for epidemiological surveillance.

BACKGROUND AND PURPOSE: Accurate data on the distribution of stroke subtypes are essential for understanding the forces driving recent morbidity and mortality trends. The introduction of diagnosis-related groups (DRGs) in the 1980s may have affected the distribution of stroke subtypes as defined by International Classification of Diseases, Ninth Revision (ICD-9), discharge diagnosis codes. METHODS: The Pawtucket Heart Health Program cardiovascular surveillance data were used to examine trends in stroke classification for 1980 to 1991 in relation to the introduction of DRGs in 2 communities in Massachusetts and Rhode Island, where DRGs were implemented 2 years apart. Included were all hospital discharges for residents aged 35 to 74 with a primary ICD-9 diagnosis of 431 to 432, 434, or 436 to 437 (N=1386 in Rhode Island, N=1839 in Massachusetts). RESULTS: In each state, concurrently with the introduction of DRGs, the proportion of strokes classified as cerebral occlusion (ICD-9 434.0 to 434.9) increased, and the proportion classified as acute but ill-defined (ICD-9 436.0 to 436.9) decreased. Before DRGs, 30.0% of strokes in Rhode Island and 26.6% in Massachusetts were classified as cerebral occlusion, whereas 51.8% in Rhode Island and 51.7% in Massachusetts were classified as acute ill defined. After DRGs were instituted, the proportions of cerebral occlusion and acute, ill-defined stroke, respectively, were 70.9% and 8.5% in Rhode Island and 74.1% and 7.7% in Massachusetts (chi(2), all P<0.001). The proportions of strokes classified as intracerebral hemorrhage or transient cerebral ischemia remained constant. CONCLUSIONS: The implementation of DRGs may have influenced coding of strokes to the ICD-9. Findings highlight the limitations of hospital discharge data for evaluating stroke subtypes and demonstrate the need for community-based surveillance for monitoring specific trends in stroke.

The disability assessment for dementia scale: a 12-month study of functional ability in mild to moderate severity Alzheimer disease.

The Disability Assessment for Dementia (DAD) scale was developed and validated as a measure of functional ability in dementia. DAD results have been reported in Alzheimer disease (AD) randomized, controlled treatment trials of up to 6 months, but results beyond 6 months have yet to be described. SAB INT 12 was a randomized, double-blind, placebo-controlled, parallel-group study in mild to moderate AD that included DAD assessments at baseline, month 6, and month 12. One hundred forty-four patients with AD in the placebo arm of SAB INT 12 were followed up for 12 months. DAD scores were obtained at baseline (mean DAD = 70.1, SD = 22.2), 6 months (mean DAD = 63.7, SD = 25.2), and 12 months (mean DAD = 59.3, SD = 28.9). The rate of decline was consistent across the domains of basic activities of daily living (ADLs) and instrumental ADLs, as well as the scoring of initiation, planning, and organization. The decline in DAD total scores in mild to moderate AD averages about one point per month, which equates to the loss of one item on the DAD scale every 2 months.

Prevalence and assessment of attention-deficit/hyperactivity disorder in primary care settings.

Research literature relating to the prevalence of attention-deficit/hyperactivity disorder (ADHD) and co-occurring conditions in children from primary care settings and the general population is reviewed as the basis of the American Academy of Pediatrics clinical practice guideline for the assessment and diagnosis of ADHD. Epidemiologic studies revealed prevalence rates generally ranging from 4% to 12% in the general population of 6 to 12 year olds. Similar or slightly lower rates of ADHD were revealed in pediatric primary care settings. Other behavioral, emotional, and learning problems significantly co-occurred with ADHD. Also reviewed were rating scales and medical tests that could be employed in evaluating ADHD. The utility of using both parent- and teacher-completed rating scales that specifically assess symptoms of ADHD in the diagnostic process was supported. Recommendations were made regarding the assessment of children with suspected ADHD in the pediatric primary care setting.

The recognition, assessment and management of dementing disorders: conclusions from the Canadian Consensus Conference on Dementia.

OBJECTIVE: i) To develop evidence based consensus statements on which to build clinical practice guidelines for primary care physicians towards the recognition, assessment and management of dementing disorders; ii) to disseminate and evaluate the impact of these statements and guidelines built on these statements. OPTIONS: Structured approach to assessment, including recommended laboratory tests, choices for neuroimaging and referral; management of complications (especially behaviour problems and depression) and use of cognitive enhancing agents. POTENTIAL OUTCOMES: Consistent and improved clinical care of persons with dementia; cost containment by more selective use of laboratory investigations, neuroimaging and referrals; appropriate use of cognitive enhancing agents. EVIDENCE: Authors of each background paper were entrusted to: perform a literature search, discover additional relevant material including references cited in retrieved articles; consult with other experts in the field and then synthesize information. Standard rules of evidence were applied. Based upon this evidence, consensus statements were developed by a group of experts, guided by a steering committee of eight individuals from the areas of Neurology, Geriatric Medicine, Psychiatry, Family Medicine, Preventive Health Care and Health Care Systems. VALUES: Recommendations have been developed with particular attention to the context of primary care and are intended to support family physicians in their ongoing assessment and care of patients with dementia. BENEFITS, HARMS AND COSTS: Potential for improved clinical care of individuals with dementia. A dissemination and evaluation strategy will attempt to measure the impact of the recommendations. RECOMMENDATIONS: See text. VALIDATION: Four other sets of consensus statements and/or guidelines have been published recently. These recommendations are generally congruent with our own consensus statements. The consensus statements have been endorsed by relevant bodies in Canada.

Effect of ethnicity on denial of authorization for emergency department care by managed care gatekeepers.

OBJECTIVE: After a pilot study suggested that African American patients enrolled in managed care organizations (MCOs) were more likely than whites to be denied authorization for emergency department (ED) care through gatekeeping, the authors sought to determine the association between ethnicity and denial of authorization in a second, larger study at another hospital. METHODS: A retrospective cohort design was used, with adjustment for triage score, age, gender, day and time of arrival at the ED, and type of MCO. RESULTS: African Americans were more likely to be denied authorization for ED visits by the gatekeepers representing their MCOs even after adjusting for confounders, with an odds ratio of 1.52 (95% CI = 1.18 to 1.94). CONCLUSIONS: African Americans were more likely than whites to be denied authorization for ED visits. The observational study design raises the possibility that incomplete control of confounding contributed to or accounted for the association between ethnicity and gatekeeping decisions. Nevertheless, the questions that these findings raise about equity of gatekeeping indicate a need for additional research in this area.

Measurement of erectile dysfunction in population-based studies: the use of a single question self-assessment in the Massachusetts Male Aging Study.

A concise, reliable means of assessing erectile dysfunction (ED) in large, multidisciplinary population-based studies is needed. A single, direct question for self-assessed ED was assessed in the population-based sample of the Massachusetts Male Aging Study (MMAS). Of the 1156 respondents to the 1995-97 MMAS follow-up evaluation, 505 were randomly selected to complete either the International Index of Erectile Function (IIEF) (n = 254), or the Brief Male Sexual Function Inventory (BMSFI) (n = 251), in addition to the single question self-assessment. The proportion not classified due to missing data was MMAS-9%, BMSFI-8%, and IIEF-18%. The single question correlated well with these other measures (r = 0.71-0.78, P < 0.001). Prevalence was similar to that based on the IIEF, agreement was moderate (kappa = 0.56-0.58), and associations with previously identified risk factors were similar for each classification. Thus, the MMAS single question may be a practical tool for population-based studies where detailed clinical measures of ED are impractical.

A fork in the road: decision time for behavioral pediatrics.

The rapid growth of managed care, and especially that of managed behavioral healthcare organizations (MBHOs), is likely to diminish the role of developmental-behavioral pediatrics and separate care for medical and behavioral problems. Thus, a rethinking of the practice of developmental-behavioral pediatrics is required. This study reviews the structure of MBHOs, identifies barriers to the provision of services by developmental-behavioral pediatricians, describes alternative practice models for consideration, and makes recommendations. The aims of the recommendations are to stimulate an active discussion about these issues, spark an advocacy effort, and ensure the continued participation of developmental-behavioral pediatricians in the care of children with special needs. The study concludes that managed care will push developmental-behavioral pediatricians into integration with primary care group practices or into specialty mental health networks. Immediate discussion, action, and advocacy will be required to ensure a presence in these decisions for developmental-behavioral pediatricians.

The recognition, assessment and management of dementing disorders: conclusions from the Canadian Consensus Conference on Dementia.

OBJECTIVE: To develop evidence based consensus statements on which to build clinical practice guidelines for primary care physicians toward the recognition, assessment and management of dementing disorders and to disseminate and evaluate the impact of these statements and guidelines built on these statements. OPTIONS: Structured approach to assessment, including recommended laboratory tests, choices for neuroimaging and referral, management of complications (especially behavioural problems and depression) and use of cognitive enhancing agents. POTENTIAL OUTCOMES: Consistent and improved clinical care of persons with dementia; cost containment by more selective use of laboratory investigations; neuroimaging and referrals; and appropriate use of cognitive enhancing agents. EVIDENCE: Authors of each background paper were entrusted to perform a literature search, discover additional relevant material, including references cited in retrieved articles, consult with other experts in the field and then synthesize information. Standard rules of evidence were applied. Based on this evidence, consensus statements were developed by a group of experts, guided by a steering committee of 8 individuals, from the areas of Neurology, Geriatric Medicine, Psychiatry, Family Medicine, Preventive Health Care and Health Care Systems. VALUES: Recommendations have been developed with particular attention to the context of primary care, and are intended to support family physicians in their ongoing assessment and care of patients with dementia. BENEFITS HARM AND COSTS: Potential for improved clinical care of people with dementia. A dissemination and evaluation strategy will attempt to measure the impact of the recommendations. RECOMMENDATIONS: Forty-eight recommendations are offered that address the following aspects of dementia care: early recognition; importance of careful history and examination in making a positive diagnosis; essential laboratory tests; rules for neuroimaging and referral; disclosure of diagnosis; importance of monitoring and providing support to caregivers; cultural aspects; detection and treatment of depression; observation and management of behavioural disturbances; detection and reporting of unsafe motor vehicle driving; genetic factors and opportunities for preventing dementia; pharmacological treatment with particular emphasis on cognitive enhancing agents. VALIDATION: Four other sets of consensus statement or guidelines have been published recently. These recommendations are generally congruent with our own consensus statements. The consensus statements have been endorsed by relevant bodies in Canada.

Evaluation of low density spine software for the assessment of bone mineral density in children.

Pediatric dual-energy X-ray absorptiometry spine scans often cannot be analyzed with standard software due to a failure to identify the bone edges of low density vertebrae. Low density spine (LDS) software improves bone detection compared with standard software. The objective of this study was to compare bone mineral density (BMD) measurements obtained with the standard and LDS software in 27 healthy nonobese, 32 obese, and 41 chronically ill children, ages 2-18 years. Lumbar spine (L1-L4) BMD, measured by standard analysis, ranged from 0.531-1.244 gm/cm2. Reanalysis with the LDS software resulted in a systematic increase (mean +/- SD) in estimated bone area of 17.0+/-5.0%, an increase in bone mineral content of 6.1+/-6.3%, and a mean decrease in BMD of 8.7+/-1.7% (all p < 0.001). This resulted in a mean decrease in BMD Z score of 0.7+/-0.2. Linear regression models, predicting standard BMD from LDS BMD, were fit for the three subject groups (R2 = 0.993-0.995). Small differences in slopes were detected across groups (p = 0.07); LDS BMD predicted higher standard BMD in obese subjects. In conclusion, LDS analysis resulted in a clinically significant decrease in measured BMD. The association between analysis methods was exceptionally high (R2 > 0.99), indicating that LDS BMD accurately predicts standard BMD. Although LDS BMD in obese subjects predicts higher standard BMD results than in nonobese subjects, the small difference is of questionable clinical significance. LDS software is a useful tool for the assessment of BMD in children.

Centralization of histocompatibility laboratories: impact on organ allocation efficiency and outcomes of cadaveric renal transplantation.

This project was undertaken to determine whether centralization of histocompatibility laboratory services for renal transplants performed within eastern Pennsylvania could improve the efficiency of allograft allocation and short-term allograft function. A nonconcurrent cohort study was performed comparing renal allografts transplanted between September 15, 1993, and September 14, 1994, to those transplanted between September 15, 1994, and September 14, 1995. All allografts were procured and allocated by the Delaware Valley Transplant Program, the organ procurement agency in eastern Pennsylvania. Cold preservation time and delayed allograft function were used to measure efficiency of allograft allocation and short term allograft function, respectively. The mean cold preservation time was reduced from 25.08 hours to 20.68 hours (P < 0.001). The percentage of delayed allograft function was 19.9 and 17.4 for the pre- and postcentralization groups, respectively (P = 0.5). Therefore, centralization of histocompatibility tissue typing was a regionally effective process intervention for reducing cold preservation time without adversely impacting short-term graft function. The magnitude of this reduction varied between individual centers. Further investigation is required to determine the effect on long-term allograft function and system wide costs.

First International Pharmacoeconomic Conference on Alzheimer's Disease: report and summary.

The First International Pharmacoeconomic Conference on Alzheimer's Disease (AD) was held in Amsterdam in July 1998. The meeting was held under the auspices of the International Working Group for Harmonization of Dementia Drug Guidelines (http://dementia.ion.ucl.ac.uk/harmon), bringing together academics, clinicians, purchasers, and representatives from industry. Presentations were given on the methodology of pharmacoeconomic studies in AD, particularly focusing on caregiver burden, quality of life (QOL), and resource utilization. Three economic models of AD were presented based on data from the United States, Canada, and the United Kingdom. In two studies, these data were then used to model the cost-effectiveness and effect on cost of treatment with donepezil. Both studies suggested a possible cost advantage for the use of donepezil, when compared with no placebo or treatment, particularly when donepezil is used appropriately in mild-to-moderate AD. These data need to be interpreted with care, as none of the cost or utility information were collected during the clinical trials. Additional data from a 2-year clinical trial of selegiline and vitamin E suggest that cognitive measures may be poor predictors of economic outcome, which is better measured directly. Both economic models of donepezil rely on short-term cognitive data to predict long-term outcome, a methodf that may not be useful in predicting economic savings. The issues facing pharmacoeconomists, researchers, clinicians, and families in the future were addressed in a series of workshops using a method of strategic futuring. The workshops attempted to see 7 years into the future for a range of areas, including consumer and caregiver use of pharmacoeconomic data; early detection and prevention; Japanese perspectives; activities of daily life and what will be daily life activities; caregiver burden; QOL at the end of life; new uses for new information and communication technology in clinical research; and physicians' use of pharmacoeconomic data. A range of exciting futures were predicted, although common themes that arose when considering barriers to achieving these futures included cost, education, political will, confidentiality, privacy, and ethics. The first conference was deemed to have been a success, having attracted more than 160 delegates and many distinguished speaker. A second conference is planned for the year 2000. Over the next 2 years, research needs to be broadened particularly in the methodological areas of resource utilization, QOL, and caregiver burden. Data from clinical trials with relevant economic and QOL outcomes will be needed by purchasers if drug treatments for dementia are to gain widespread use. It is also hoped that the models described at the meeting may become more freely available to politicians, purchasers, clinicians, and caregivers to help them make better decisions about treatment.