Randomized clinical trial of liposomal bupivacaine transverse abdominis plane block versus intrathecal analgesia in colorectal surgery.

BACKGROUND: Transverse abdominis plane (TAP) block is considered an effective alternative to neuraxial analgesia for abdominal surgery. However, limited evidence supports its use over traditional analgesic modalities in colorectal surgery. This study compared the analgesic efficacy of liposomal bupivacaine TAP block with intrathecal (IT) opioid administration in a multicentre RCT. METHODS: Patients undergoing elective small bowel or colorectal resection were randomized to receive TAP block or a single injection of IT analgesia with hydromorphone. Patients were assessed at 4, 8, 16, 24 and 48 h after surgery. Primary outcomes were mean pain scores and morphine milligram equivalents (MMEs) administered within 48 h after surgery. Secondary outcomes included duration of hospital stay, incidence of postoperative ileus and use of intravenous patient-controlled analgesia. RESULTS: In total, 209 patients were recruited and 200 completed the trial (TAP 102, IT 98). The TAP group had a 1·6-point greater mean pain score than the IT group at 4 h after surgery, and this difference lasted for 16 h after operation. The TAP group received more MMEs within the first 24 h after surgery than the IT group (median difference in MMEs 10·0, 95 per cent c.i. 3·0 to 20·5). There were no differences in MME use at 24 and 48 h, or with respect to secondary outcomes. CONCLUSION: IT opioid administration provided better immediate postoperative pain control than TAP block. Both modalities resulted in low pain scores in patients undergoing elective colorectal surgery and should be considered in multimodal postoperative analgesic plans. Registration number: NCT02356198 ( http://www.clinicaltrials.gov).

IgG antibodies from dourine infected horses identify a distinctive Trypanosoma equiperdum antigenic pattern of low molecular weight molecules.

Diagnosis and control of dourine is strongly based on serological evidence, but knowledge of the humoral response of horses during infection is limited. In this study we developed a chemiluminescent immunoblotting (cIB) assay to characterise the Trypanosoma equiperdum antigen pattern recognised by IgGs from naturally or experimentally dourine-infected horses and analyse the kinetics of IgG humoral response following the infection. One compounding factor is that sera from uninfected animals often cross-react with T. equiperdum antigens. Development of the cIB assay was based on the hypothesis that serum IgGs from healthy and infected animals recognise different T. equiperdum antigen patterns. We used sera from 8 naturally infected horses which had recovered from Italian outbreaks and 2 experimentally infected mares. In addition, sera from 10 healthy control animals, eight of which were CFT positive but IFA negative for dourine, were collected from disease free regions. Sera were compared by the complement fixation test (CFT), indirect immune fluorescence (IFA) and the cIB assay. cIB analysis revealed that IgGs from infected horses, in contrast to IgGs from healthy horses, specifically recognise a T. equiperdum antigenic profile with low molecular weight bands ranging between 16 and 35 kDa. A time course experiment indicated that IgGs specific for the 16-35 kDa parasite protein fraction appear 17 days post-infection. The cIB assay confirmed all ten infected animals as positive and all controls as negative. This study demonstrated that analysis of IgGs by cIB can provide clear confirmation of trypanosome infection in horses, suggesting that this technique can be applied as a confirmatory serological test for dourine infection.

Do pre-existing complications affect the failure to rescue quality measures?

BACKGROUND: A project sponsored by the University Health System Consortium has addressed the inaccuracy and high variability across institutions concerning the use of the failure to rescue (FTR) quality indicator defined by the Agency for Healthcare Research and Quality (AHRQ). Results indicated that of the complications identified by the quality indicator, 29.5% were pre-existing upon hospital admission. OBJECTIVE: The purpose of our study was to investigate the possible bias to FTR measures by including cases of complications that were pre-existing at admission. METHODS: Hospital discharges between 1 January 1996 and 30 September 2007 were retrospectively gathered from administrative databases. Using definitions outlined by the AHRQ and the National Quality Forum (NQF), FTR rates were calculated. Using present on admission coding, FTR rates were recalculated to differentiate between the rates of pre-existing and that of acquired cases. RESULTS: Using the AHRQ definition, the overall FTR rate was 11.60%. The FTR rate for patients with pre-existing complications was 8.85%, whereas patients with complications acquired during hospitalisation had an FTR rate of 18.46% (p<0.001). The NQF FTR rate was 9.93%. Pre-existing and acquired FTR rates using the NQF measure were 9.42% and 12.77%, respectively (p<0.001). CONCLUSIONS: Current definitions of FTR measures meant to identify inhospital complications appear biased by the inclusion of problems at admission. Furthermore, many patients with these complications are excluded from the algorithms. When taking into account the timing of the "complications", these measures can be useful for internal quality control. However, it should be stressed that the usefulness of the measures to compare institutions will be dependent on coding practices of institutions. Validation using chart review may be required.

Demonstration of differences in virulence between two Theileria parva isolates.

In areas with a low incidence of infection due to unimodal presence of ticks, Theileria parva has been observed to induce a disease with relatively low pathology. This is followed by a carrier state, rather than death and therefore provides a better chance of transmission of the parasite back to the tick vector since in unimodal conditions, the different tick stages occur at different times. One isolate from such an area in Zambia, T. parva Chitongo, was compared for virulence with T. parva Muguga, isolated from an area exhibiting a continuous presence of all vector stages in East Africa. To reduce any variation due to infection dose, an in vitro standardized dose was used to initiate infection of groups of three local zebu cattle with each isolate. Parameters of virulence measured were prepatent period, fever, survival (based on ECF index), parasitosis, piroplasm parasitaemia and hematological parameters. Our results suggest that T. parva Chitongo developed a slightly later onset (1-2 days) and lower levels of parasitosis in the lymph node, causing less and later mortality. Comparison of the in vitro rate of transformation confirmed that the time needed to transform an infected lymphocyte took 4 days longer for T. parva Chitongo than T. parva Muguga. Elucidating the mechanism responsible for the lower virulence of T. parva Chitongo could be useful for designing an attenuated vaccine.

Medication reconciliation in ambulatory care: attempts at improvement.

OBJECTIVE: To enhance overall accuracy of medication lists by providing performance feedback and training to the healthcare team and increasing patient participation in the medication reconciliation process. METHODS: This prospective study involved patients seen in four academic, ambulatory primary care internal medicine clinics. Before the interventions, baseline data were analysed, assessing completeness, correctness and accuracy of medication documentation in the electronic medical record. Interventions to provide performance feedback and training to the healthcare team, increase patient awareness and participation in the medication reconciliation process were implemented. Immediately after each intervention, a data collection was undertaken to assess the effectiveness of the intervention on the accuracy of individual medications and medication lists. RESULTS: Completeness of medication lists improved from 20.4% to 50.4% (p<0.001). The incomplete documentation of medication lists was mostly because of lack of frequency (15.4%) and route (8.9%) for individual medications within a medication list. Correctness of medication lists improved from 23.1% to 37.7% (p = 0.087). The incorrectness in a medication list was mostly because of incorrect medications dose. Patient participation in the medication reconciliation process increased from 13.9% to 33% (p<0.001). The medication list accuracy improved from 11.5% to 29% (p = 0.014). CONCLUSION: In this setting, it was helpful to engage the active participation of all members of the healthcare team and most importantly the patient to improve the accuracy of medication lists.

Gene expression profiling in a mouse model for African trypanosomiasis.

This study aimed to provide the foundation for an integrative approach to the identification of the mechanisms underlying the response to infection with Trypanosoma congolense, and to identify pathways that have previously been overlooked. We undertook a large-scale gene expression analysis study comparing susceptible A/J and more tolerant C57BL/6 mice. In an initial time course experiment, we monitored the development of parasitaemia and anaemia in every individual. Based on the kinetics of disease progression, we extracted total RNA from liver at days 0, 4, 7, 10 and 17 post infection and performed a microarray analysis. We identified 64 genes that were differentially expressed in the two strains in non-infected animals, of which nine genes remained largely unaffected by the disease. Gene expression profiling at stages of low, peak, clearance and recurrence of parasitaemia suggest that susceptibility is associated with high expression of genes coding for chemokines (e.g. Ccl24, Ccl27 and Cxcl13), complement components (C1q and C3) and interferon receptor alpha (Ifnar1). Additionally, susceptible A/J mice expressed higher levels of some potassium channel genes. In contrast, messenger RNA levels of a few immune response, metabolism and protease genes (e.g. Prss7 and Mmp13) were higher in the tolerant C57BL/6 strain as compared to A/J.

Bovine trypanotolerance: A natural ability to prevent severe anaemia and haemophagocytic syndrome?

Trypanotolerance is the capacity of certain West-African, taurine breeds of cattle to remain productive and gain weight after trypanosome infection. Laboratory studies, comparing Trypanosoma congolense infections in trypanotolerant N'Dama cattle (Bos taurus) and in more susceptible Boran cattle (Bos indicus), confirmed the field observations. Experiments using haemopoietic chimeric twins, composed of a tolerant and a susceptible co-twin, and T cell depletion studies suggested that trypanotolerance is composed of two independent traits. The first is a better capacity to control parasitaemia and is not mediated by haemopoietic cells, T lymphocytes or antibodies. The second is a better capacity to limit anaemia development and is mediated by haemopoietic cells, but not by T lymphocytes or antibodies. Weight gain was linked to the latter mechanism, implying that anaemia control is more important for survival and productivity than parasite control. Anemia is a marker for a more complex pathology which resembles human haemophagocytic syndrome: hepatosplenomegaly, pancytopenia and a large number of hyperactivated phagocytosing macrophages in bone marrow, liver and other tissues. Thus, mortality and morbidity in trypanosome-infected cattle are primarily due to self-inflicted damage by disproportionate immune and/or innate responses. These features of bovine trypanotolerance differ greatly from those in murine models. In mice, resistance is a matter of trypanosome control dependent on acquired immunity. However, a model of anaemia development can be established using C57BL/6J mice. As in cattle, the induction of anaemia was independent of T cells but its development differed with different trypanosome strains. Identification of the molecular pathways that lead to anaemia and haemophagocytosis should allow us to design new strategies to control disease.

Pathology of Tnf-deficient mice infected with Plasmodium chabaudi adami 408XZ.

Tumor necrosis factor alpha (Tnf) plays a pleiotropic role in murine malaria. Some investigations have correlated Tnf with hypothermia, hyperlactatemia, hypoglycemia, and a suppression of the erythropoietic response, although others have not. In this study, we have evaluated parasitemia, survival rate and several pathological features in C57BL/6JTnf(-/-) and C57BL/6JTnf(+/+) mice after infection with Plasmodium chabaudi adami 408XZ. Compared to the C57BL/6JTnf(+/+) mice, C57BL/6JTnf(-/-) mice showed increased parasitemia and decreased survival rate, whereas blood glucose, blood lactate and body weight were not significantly different. However, C57BL/6JTnf(-/-) mice suffered significantly more from severe anemia and hypothermia than C57BL/6JTnf(+/+) mice. These results suggest that Tnf is an important mediator of parasite control, but not of anemia development. We hypothesize that the high mortality observed in the Tnf knock-out mice is due to increased anemia and pathology as a direct result of increased levels of parasitemia.

TNF-alpha mediates the development of anaemia in a murine Trypanosoma brucei rhodesiense infection, but not the anaemia associated with a murine Trypanosoma congolense infection.

Development of anaemia in inflammatory diseases is cytokine-mediated. Specifically, the levels of tumour necrosis factor-alpha (TNF-alpha), produced by activated macrophages, are correlated with severity of disease and anaemia in infections and chronic disease. In African trypanosomiasis, anaemia develops very early in infection around the time when parasites become detectable in the blood. Since the anaemia persists after the first waves of parasitaemia when low numbers of trypanosomes are circulating in the blood, it is generally assumed that anaemia is not directly induced by a parasite factor, but might be cytokine-mediated, as in other cases of anaemia accompanying inflammation. To clarify the role of TNF-alpha in the development of anaemia, blood parameters of wild type (TNF-alpha+/+), TNF-alpha-null (TNF-alpha-/-) and TNF-alpha-hemizygous (TNF-alpha-/+) trypanotolerant mice were compared during infections with the cattle parasite Trypanosoma congolense. No differences in PCV, erythrocyte numbers or haemoglobin were observed between TNF-alpha-deficient and wild type mice, suggesting that the decrease in erythrocytes was not mediated by TNF-alpha. Erythropoetin (EPO) levels increased during infection and no significant differences in EPO levels were observed between the three mouse strains. In contrast, during an infection with the human pathogen Trypanosoma brucei rhodesiense, the number of red blood cells in TNF-alpha-deficient mice remained significantly higher than in the wild type mice. These data suggest that more than one mechanism promotes the development of anaemia associated with trypanosomiasis.

Comparison of pathology in susceptible A/J and resistant C57BL/6J mice after infection with different sub-strains of Plasmodium chabaudi.

Susceptible A/J and more resistant C57BL/6J mice were infected with Plasmodium chabaudi chabaudi 54X, P.c. chabaudi AS and Plasmodium chabaudi adami 408XZ. As expected, most C57BL/6J mice survived the infections with the different isolates. But in contrast to previous observations, not all A/J mice succumbed to infection: just over 50% of A/J mice survived infections with P.c. chabaudi 54X, while 80% survived P.c. chabaudi AS. The more virulent parasite, P.c. adami 408XZ, was able to kill all A/J mice and 20% of C57BL/6J mice after an intravenous infection with 10(5) pRBC. A detailed study of four parameters of pathology (body weight, body temperature, blood glucose and RBC counts) in both mouse strains after a P.c. adami 408XZ infection showed similar patterns to those previously reported after infection with P.c. chabaudi AS. These data suggest that environmental factors as well as parasite polymorphisms might influence the severity of malaria between susceptible and resistant mice.

Identification of mechanisms of natural resistance to African trypanosomiasis in cattle.

Natural resistance to African trypanosomiasis in certain Bos taurus cattle in West Africa, called trypanotolerance, may hold solutions for control of this economically crippling disease. Comparison of immune responses between trypanotolerant and trypanosusceptible cattle have shown some differences in antibody response, complement level and cytokine expression, but it is not known whether these differences are the cause of resistance. Two experiments were carried out to assess the contribution of the immune and haemopoietic systems to trypanotolerance. The production of haemopoietic chimaeras from trypanotolerant and susceptible twin calves and comparison of their responses after infection with singleton calves, allowed an assessment of the role of the haemopoietic system in trypanotolerance. An in vivo depletion of CD4 cells in the two breeds allowed an appraisal of the role of T and B lymphocytes in trypanotolerance. The results of the two experiments suggest that natural resistance comprises at least two mechanisms, an innate mechanism that controls parasite growth, and another, involving the haemopoietic system, that is able to limit anaemia. This supports the hypothesis that innate mechanisms in trypanotolerant cattle are more efficient in controlling disease, making them less reliant on antibody responses.

Screening mammogram utilization in women with diabetes.

OBJECTIVE: To determine whether women with diabetes undergo fewer screening mammograms than matched control subjects. RESEARCH DESIGN AND METHODS: A total of 424 women with diabetes aged 50-75 years who received their primary care from general internists at a large Midwestern multispecialty group practice were retrospectively studied for frequency of mammography from August 1997 to January 2000. Two control subjects without diabetes (n = 845) were matched to each case by age, sex, provider, and date of visit. The main outcome measure was the percentage of subjects undergoing mammography 1 year before and 30 days after an index date, defined as the most recent health care visit after August 1997 and before January 2000. RESULTS: Analysis by conditional logistic regression demonstrated that women with diabetes had significantly lower rates of mammograms than control subjects (78.1 vs. 84.9%, respectively; odds ratio 0.63, P = 0.002). After adjusting for insurance status and race, women with diabetes continued to have significantly lower rates of mammography (odds ratio 0.70, P = 0.027). CONCLUSIONS: Women with diabetes were significantly less likely to undergo screening mammography than control subjects. Considering the increasing incidence of diabetes and the equal incidence of malignancy in women with and without diabetes, it would be beneficial to improve breast cancer screening in this population.

Identity of activation molecule 3 on superantigen-stimulated bovine cells is CD26.

Most CD8(+) T cells in cultures of bovine mononuclear cells stimulated with staphylococcal enterotoxin C1 develop an unusual phenotype characterized by expression of activation molecule 3 (ACT3). This superantigen-dependent phenotype may be relevant to immunopathogenesis mediated by certain microbial toxins. The size and N-terminal sequence of immunoprecipitated ACT3 indicate that ACT3 is the bovine orthologue of CD26.

An accessory role for the diacylglycerol moiety of variable surface glycoprotein of African trypanosomes in the stimulation of bovine monocytes.

The membrane-associated form of the variable surface glycoprotein (mfVSG) from African trypanosomes is a potent macrophage activator capable of inducing production of tumor necrosis factor alpha (TNFalpha) in both bovine and murine models. Using a bovine model, we have re-investigated the hypothesis that the diacylglycerol moiety of the glycosylphosphatodylinositol (GPI) anchor is involved in macrophage activation and might be the actual parasite toxin. The anchor of the variable surface glycoprotein (VSG) was labeled with (3)H-myristic acid and VSG purified in its membrane-associated form. The dimyristylglycerol moiety of the anchor was released by phospholipase C cleavage. Integrity of the anchor and efficiency of cleavage was verified by autoradiography and methanol:hexane extraction. For analysis of biological function, bovine monocytes were used which had been incubated with bovine interferon gamma (primed) or with culture medium (unprimed). The VSG purified in its membrane-associated form was found to stimulate both primed and unprimed cells to secrete TNFalpha. The same preparation from which the dimyristylglycerol moiety had been cleaved was no longer able to stimulate unprimed cells but could still stimulate primed cells. Our data indicate that the presence of the dimyristylglycerol is not an absolute requirement for induction of TNFalpha production but can substitute for the interferon gamma priming. Therefore, we favor the hypothesis that stimulation of macrophages to secrete TNFalpha by the mfVSG is mediated by an as yet unknown trigger moiety and is facilitated by the dimyristylglycerol anchor.

Improving hypertension control: a team approach in a primary care setting.

BACKGROUND: Blood pressure (BP) control rates in the United States have not improved significantly during the past decade. There has been limited study of improvement efforts focusing on guideline implementation and changes in the model of care to address hypertension. METHODS: Five physician (MD)/registered nurse (RN)/licensed practical nurse (LPN) teams in a large community practice modified their care model in 1997 to manage hypertensive patients as part of guideline implementation efforts. The other 25 MD teams in the same setting practiced in the usual model, but were exposed to the guideline recommendations. BP control rates of patients in each group were assessed monthly. After nine months of testing the new care model, 10 additional teams adopted the model. RESULTS: In the pilot group, hypertension control rates showed statistically significant improvement from pre- (33.1%) to postimplementation (49.7%). After adjusting for age, this was significantly greater than the improvement in the control group (p = 0.033). Medication changes were more frequent in the pilot group (32.3%) than in the control group (27.6%); however, the differences were not statistically significant. A longitudinal examination of the hypertension patients in the study showed that improved BP control was sustained for at least 12 months. DISCUSSION: A change in the model of care for hypertensive patients within a primary care practice resulted in significant, sustainable improvement in BP control rates. These changes are consistent with the chronic care model developed by Wagner; practice redesign appeared to be the most important change.

Managing the primary care practice on the Web

Physicians and administrators have little hope of responding appropriately to the challenges of the health care market without data to support decision making. Desired Mayo Clinic s Primary Care Practice was to have the ability to access and integrate data from many platforms in many formats from the Enterprise and bring this information to the desktop in a robust interactive display. The solution was delivery of the data to the Web through an interface using Java with access to Online Analytical Processing (OLAP) tools for summarization, graphical display and reporting. Communicating major trends, assisting in planning and management, visually displaying alerts in summary data and individual patients that are all possible through an easy-to-use Web application. To really understand what the summarized data represents, the physicians must be able to drill down, download and explore their own detail data. A pilot project was developed to test the capabilities of the development environment, the acceptance Web tools, the ability to deliver timely information and the methodology of using a multi-dimensional database to define the data. The Family Medicine practice at four separate locations was chosen for the demonstration project. Two practices in Rochester, MN and practices in two smaller towns, totaling 50 physicians and administrative personnel, were the first clients using the system. A cross-functional team examined a variety of development issues such as data sources, data definitions, levels of security, data analysis types, and style of display. Demonstrations of the prototype met with an overwhelming positive response from administrators and department leaders. The Physician Patient Management solution collects, analyzes, and communicates the information needed to meet today s health care challenges.

Busy physicians and preventive services for adults.

OBJECTIVE: To study the relationship between overall productivity and the rates at which primary care physicians, in a fee-for-service setting, deliver or prescribe preventive services to adult patients. PATIENTS AND METHODS: The charts of 452 adult patients treated by 8 family practitioners and 5 internists in a fee-for-service practice setting were randomly selected and abstracted for provision of 10 preventive services over a 27-month period. The percentage of eligible patients screened for each service was correlated with the production of each physician measured in relative value units (RVUs). RESULTS: The correlation coefficient between RVUs and the aggregate of the 10 services was 0.23 (95% confidence interval [CI], -0.36 to 0.70). The individual correlation coefficients between RVUs and 9 of the 10 preventive services ranged from -0.05 to 0.43. For cervical cancer screening, however, the correlation coefficient was -0.72 (95% CI, -0.91 to -0.24). CONCLUSION: With the exception of screening for cervical cancer, the data presented in this study do little to support physicians' common belief that lack of time is the reason they are unable to incorporate prevention strategies into their clinical practice.

Improving performance in diabetes care: a multicomponent intervention.

CONTEXT: Compliance with recommendations from the American Diabetes Association for management of patients with diabetes is not optimal. Changing physician practice patterns with provider-focused interventions can be difficult. We report results after implementation of a type 2 diabetes mellitus guideline. OBJECTIVE: To increase the annual rate of microalbumin/urine protein testing, dilated eye examinations, and foot examinations for patients with diabetes and to reduce overall levels of hemoglobin A1c (Hb A1c). DESIGN: Before-after study. INTERVENTION: From April 1996 to June 1998, a guideline on type 2 diabetes mellitus was implemented with multicomponent interventions. These included small group educational sessions led by opinion leaders, an electronic version of the guideline, audit with feedback, and enhanced clinical orders support. Medical records of random samples of patients with diabetes were audited for specific diabetes performance measures on a monthly basis. Baseline data were compared with results at the end of the implementation effort. SETTING: Southeastern Minnesota, excluding Olmsted County. PARTICIPANTS: Adult patients seen at one practice of 18 general internists. OUTCOME MEASURES: Outcome measures included Hb A1c values and annual performance of a urine protein test, foot examination, and dilated eye examination. RESULTS: Gradual, sustained; and statistically significant improvements in the three annual performance measures were observed. Urine protein testing increased from 24% to 66% (P = 0.001), dilated eye examinations increased from 63% to 84% (P = 0.001), and foot examinations increased from 86% to 97% (P = 0.001). Mean Hb A1c values +/- SD also improved from 7.8% +/- 1.0% to 7.1% +/- 0.7% (P < 0.001) in patients who received continuing care for diabetes. CONCLUSIONS: Statistically significant improvements were observed after continuous improvement efforts were focused on providers in an individual group practice. When used to implement a diabetes guideline, such interventions may improve delivery of services and reduce Hb A1c levels in patients with diabetes.

Trypanosome non-specific IgM antibodies detected in serum of Trypanosoma congolense-infected cattle are polyreactive.

Serum Ig from Trypanosoma congolense-infected cattle were affinity-purified using immobilised trypanosome or non-trypanosome antigens (beta-galactosidase, cytochrome C and ferritin). The bound and unbound IgG and IgM fractions were collected and tested in ELISA for reactivity to each antigen. The results indicated that the presence of reactivity to non-parasite antigens in serum of infected cattle is due to polyreactive IgM antibodies. However, the IgG fraction only bound to trypanosome antigens and was only present in post-infection sera, indicating that it was induced by the infecting trypanosomes. Since the polyreactive IgM antibodies were also present in pre-infection sera, it is probable that they were natural antibodies that were not induced but only amplified by the trypanosome infection.

Traumatic brain injury and time to onset of Alzheimer's disease: a population-based study.

Controversy continues as to whether traumatic brain injury is a risk factor for Alzheimer's disease. The authors examined a related hypothesis that among persons with traumatic brain injury who develop Alzheimer's disease, time to onset of the disease is reduced. They used data on all documented episodes of traumatic brain injury that occurred from 1935 to 1984 among Olmsted County, Minnesota, residents. Community-based medical records were used to follow traumatic brain injury cases who were aged 40 years or older at last contact prior to June 1, 1988, for Alzheimer's disease until last contact, death, or June 1, 1988. The test of the hypothesis was restricted to those cases who developed Alzheimer's disease. The expected time to onset of Alzheimer's disease was derived from a life table constructed by using age-of-onset distributions within sex groups for a previously identified cohort of Rochester, Minnesota, Alzheimer's disease incidence cases without a history of head trauma. The authors found that of the 1,283 traumatic brain injury cases followed, 31 developed Alzheimer's disease, a number similar to that expected (standardized incidence ratio = 1.2, 95% confidence interval 0.8-1.7). However, the observed time from traumatic brain injury to Alzheimer's disease was less than the expected time to onset of Alzheimer's disease (median = 10 vs. 18 years, p = 0.015). The results suggest that traumatic brain injury reduces the time to onset of Alzheimer's disease among persons at risk of developing the disease.