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1.  Segmentation of the Canine Corpus Callosum using Diffusion Tensor Imaging Tractography 
We set out to determine functional white matter (WM) connections passing through the canine corpus callosum useful for subsequent studies of canine brains that serve as models for human WM pathway disease. Based on prior studies, we anticipated that the anterior corpus callosum would send projections to the anterior cerebral cortex while progressively posterior segments would send projections to more posterior cortex.
A post mortem canine brain was imaged using a 7T MRI producing 100 micron isotropic resolution DTI analyzed by tractography. Using ROIs within cortical locations, which were confirmed by a Nissl stain that identified distinct cortical architecture, we successfully identified 6 important WM pathways. We also compared fractional anisotropy (FA), apparent diffusion coefficient (ADC), radial diffusivity (RD), and axial diffusivity (AD) in tracts passing through the genu and splenium.
Callosal fibers were organized based upon cortical destination, i.e. fibers from the genu project to the frontal cortex. Histologic results identified the motor cortex based on cytoarchitectonic criteria that allowed placement of ROIs to discriminate between frontal and parietal lobes. We also identified cytoarchitecture typical of the orbital frontal, anterior frontal, and occipital regions and placed ROIs accordingly. FA, ADC, RD and AD values were all higher in posterior corpus callosum fiber tracts.
Using 6 cortical ROIs, we identified 6 major white matter tracts that reflect major functional divisions of the cerebral hemispheres and we derived quantitative values that can be used for study of canine models of human WM pathological states.
PMCID: PMC3998204  PMID: 24370161
2.  Automated use of WHONET and SaTScan to detect outbreaks of Shigella spp. using antimicrobial resistance phenotypes 
Epidemiology and infection  2009;138(6):873-883.
Antimicrobial resistance is a priority emerging public health threat, and the ability to detect promptly outbreaks caused by resistant pathogens is critical for resistance containment and disease control efforts. We describe and evaluate the use of an electronic laboratory data system (WHONET) and a space–time permutation scan statistic for semi-automated disease outbreak detection. In collaboration with WHONET-Argentina, the national network for surveillance of antimicrobial resistance, we applied the system to the detection of local and regional outbreaks of Shigella spp. We searched for clusters on the basis of genus, species, and resistance phenotype and identified 19 statistical ‘events’ in a 12-month period. Of the six known outbreaks reported to the Ministry of Health, four had good or suggestive agreement with SaTScan-detected events. The most discriminating analyses were those involving resistance phenotypes. Electronic laboratory-based disease surveillance incorporating statistical cluster detection methods can enhance infectious disease outbreak detection and response.
PMCID: PMC4093803  PMID: 19796449
Antibiotic resistance; medical informatics; outbreaks; Shigella; surveillance
4.  Using encounters versus episodes in syndromic surveillance 
Automated electronic medical records may be useful for syndromic surveillance to quickly detect infectious disease outbreaks. Some syndromic surveillance systems include every encounter in the analysis, whereas others exclude individuals' repeat encounters within the same syndrome occurring within a short period of time, with the rationale that these represent follow-up visits rather than new episodes of illness.
We evaluate the effect of keeping all encounters as compared with removing repeat encounters. Using the prospective space–time permutation scan statistic, we performed daily analyses on all encounters versus on episodes defined as encounters new within 2, 6 or 12 weeks. Data were taken from a Massachusetts Health Maintenance Organization (HMO) for the calendar year 1999 for four different syndromes.
We found extensive disagreement in the number of signals detected: 70, 68, 21 and 15 signals when using all encounters versus 15–20, 3, 4–5 and 0 signals when using only new episodes for lower respiratory, lower gastrointestinal, upper gastrointestinal and neurologic syndromes, respectively.
Using all encounters in syndromic surveillance may not only create too many signals but may also miss some signals by masking the anomalies generated by actual episodes. However, it is also possible to miss signals when using episodes.
PMCID: PMC2781720  PMID: 19443438
gastrointestinal; lower respiratory; neurologic; space–time surveillance
5.  Sex differences in gout epidemiology: evaluation and treatment 
Annals of the Rheumatic Diseases  2006;65(10):1368-1372.
Little is known about the characteristics, evaluation and treatment of women with gout.
To examine the epidemiological differences and differences in treatment between men and women in a large patient population.
The data from approximately 1.4 million people who were members of seven managed care plans in the USA for at least 1 year between 1 January 1999 and 31 December 2003 were examined. Adult members who had pharmacy benefits and at least two ambulatory claims specifying a diagnosis of gout were identified. In addition, men and women who were new users of urate‐lowering drugs (ULDs) were identified to assess adherence with recommended surveillance of serum urate levels within 6 months of initiating urate‐lowering treatment.
A total of 6133 people (4975 men and 1158 women) with two or more International Classification of Disease‐9 codes for gout were identified. As compared with men with gout, women were older (mean age 70 (SD 13) v 58 (SD 14), p<0.001) and had comorbidities and received diuretics more often (77% v 40%; p<0.001). Only 37% of new users of urate‐lowering treatment had appropriate surveillance of serum urate levels post‐initiation of urate‐lowering treatment. After controlling for age, comorbidities, gout treatments, number of ULD dispensings and health plan, women were more likely (odds ratio 1.36, 95% confidence interval 1.11 to 1.67) to receive the recommended serum urate level testing.
Women with gout were older, had greater comorbidities and more often used diuretics and received appropriate surveillance of serum urate levels, suggesting that the factors leading to gout as well as monitoring of treatment are very different in women and men.
PMCID: PMC1798311  PMID: 16644784
6.  Quality of information on risk factors reported by ski patrols 
Injury Prevention  2004;10(5):275-279.
Objective: To determine the reliability of reporting of information on risk factors from a standard accident report form used by ski patrols and a follow up mail questionnaire or telephone interview among injured skiers and snowboarders.
Setting: 19 ski areas in the Canadian province of Quebec between November 2001 and April 2002.
Participants: 4377 injured skiers and snowboarders seen by the ski patrol, who completed a follow up mail questionnaire or telephone interview.
Main outcome measures: κ and weighted κ statistics were used to measure the chance corrected agreement for self reported ability, age, skiing time on day of injury, lessons, type of practice, use of helmet at time of injury, and hill difficulty.
Results: The κ value for helmet use at the time of injury was 0.88 (95% confidence interval 0.87 to 0.90) and for other risk factors ranged from 0.45 (skiing time on day of injury) to 0.98 (age). Few differences were seen in reporting by body region of injury. Reporting consistency was lower for respondents who completed telephone interviews compared with those who completed mail questionnaires and those who responded more than four months after the injury.
Conclusions: Moderate to almost perfect agreement, depending on the risk factor, exists between ski patrols' accident report forms and follow up information. Ski patrol reports can be a reliable and readily available source of information on risk factors for skiing and snowboarding.
PMCID: PMC1730137  PMID: 15470006
7.  Seasonal congestive heart failure mortality and hospitalisation trends, Quebec 1990–1998 
Study objective: To describe seasonal congestive heart failure (CHF) mortality and hospitalisations in Quebec, Canada between 1990–1998 and compare trends in CHF mortality and morbidity with those in France.
Design: Population cohort study.
Setting: Province of Quebec, Canada.
Patients: Mortality data were obtained from the Quebec Death Certificate Registry and hospitalisation from the Quebec Med-Echo hospital discharge database. Cases with primary ICD-9 code 428 were considered cases of CHF.
Results: Monthly CHF mortality was higher in January, declined until September and then rose steadily (p<0.05). Hospital admissions for CHF declined from May until September (moving averages analysis p<0.0001). Seasonal mortality patterns observed in Quebec were similar to those observed in France.
Conclusion: CHF mortality in Quebec is highest during the winter and declines in the summer, similar to observations in France and Scotland. This suggests that absolute temperatures may not necessarily be that important but increased CHF mortality is observed once environmental temperatures fall below a certain "threshold" temperature. Alternatively better internal heating and warmer clothing required for survival in Quebec may ameliorate mortality patterns despite colder external environments.
PMCID: PMC1732686  PMID: 14729893
8.  Epidemiology of and surveillance for postpartum infections. 
Emerging Infectious Diseases  2001;7(5):837-841.
We screened automated ambulatory medical records, hospital and emergency room claims, and pharmacy records of 2,826 health maintenance organization (HMO) members who gave birth over a 30-month period. Full-text ambulatory records were reviewed for the 30-day postpartum period to confirm infection status for a weighted sample of cases. The overall postpartum infection rate was 6.0%, with rates of 7.4% following cesarean section and 5.5% following vaginal delivery. Rehospitalization; cesarean delivery; antistaphylococcal antibiotics; diagnosis codes for mastitis, endometritis, and wound infection; and ambulatory blood or wound cultures were important predictors of infection. Use of automated information routinely collected by HMOs and insurers allows efficient identification of postpartum infections not detected by conventional surveillance.
PMCID: PMC2631873  PMID: 11747696
9.  Clinical consequences and cost of limiting use of vancomycin for perioperative prophylaxis: example of coronary artery bypass surgery. 
Emerging Infectious Diseases  2001;7(5):820-827.
Routine us of vancomycin for perioperative prophylaxis is discouraged, principally to minimize microbial resistance to it. However, outcomes and costs of this recommendation have not been assessed. We used decision-analytic models to compare clinical results and cost-effectiveness of no prophylaxis, cefazolin, and vancomycin, in coronary artery bypass graft surgery. In the base case, vancomycin resulted in 7% fewer surgical site infections and 1% lower all-cause mortality and saved $117 per procedure, compared with cefazolin. Cefazolin, in turn, resulted in substantially fewer infections and deaths and lower costs than no prophylaxis. We conclude that perioperative antibiotic prophylaxis with vancomycin is usually more effective and less expensive than cefazolin. Data on vancomycin's impact on resistance are needed to quantify the trade-off between individual patients' improved clinical outcomes and lower costs and the future long-term consequences to society.
PMCID: PMC2631870  PMID: 11747694
10.  Intraoperative redosing of cefazolin and risk for surgical site infection in cardiac surgery. 
Emerging Infectious Diseases  2001;7(5):828-831.
Intraoperative redosing of prophylactic antibiotics is recommended for prolonged surgical procedures, although its efficacy has not been assessed. We retrospectively compared the risk of surgical site infections in 1,548 patients who underwent cardiac surgery lasting >240 min after preoperative administration of cefazolin prophylaxis. The overall risk of surgical site infection was similar among patients with (43 [9.4%] of 459) and without (101 [9.3%] of 1,089) intraoperative redosing (odds ratio [OR] 1.01, 95% confidence interval [CI] 0.70-1.47). However, redosing was beneficial in procedures lasting >400 min: infection occurred in 14 (7.7%) of 182 patients with redosing and in 32 (16.0%) of 200 patients without (adjusted OR 0.44, 95% CI 0.23-0.86). Intraoperative redosing of cefazolin was associated with a 16% reduction in the overall risk for surgical site infection after cardiac surgery, including procedures lasting <240 min.
PMCID: PMC2631868  PMID: 11791504
11.  Exploratory analysis: what to do first 
Injury Prevention  1998;4(2):140.
PMCID: PMC1730367  PMID: 9666370
12.  Automated methods for surveillance of surgical site infections. 
Emerging Infectious Diseases  2001;7(2):212-216.
Automated data, especially from pharmacy and administrative claims, are available for much of the U.S. population and might substantially improve both inpatient and postdischarge surveillance for surgical site infections complicating selected procedures, while reducing the resources required. Potential improvements include better sensitivity, less susceptibility to interobserver variation, more uniform availability of data, more precise estimates of infection rates, and better adjustment for patients' coexisting illness.
PMCID: PMC2631728  PMID: 11294709
13.  Can managed health care help manage health care-associated infections? 
Emerging Infectious Diseases  2001;7(2):358-362.
Managed-care organizations have a unique opportunity, still largely unrealized, to collaborate with health-care providers and epidemiologists to prevent health care-associated infections. Several attributes make these organizations logical collaborators for infection control programs: they have responsibility for defined populations of enrollees and for their overall health, including preventive care; they possess unique data resources about their members and their care; and they are able to make systemwide changes in care. Health care-associated infections merit the attention and effort of managed-care organizations because these infections are common, incur substantial illness and costs, and can be effectively prevented by using methods that are unevenly applied in different health-care settings. Both national and local discussions will be required to enable the most effective and efficient collaborations between managed care organizations and health-care epidemiologists. It will be important to articulate clear goals and standards that can be readily understood and widely adopted.
PMCID: PMC2631722  PMID: 11294740
14.  ANOVA, t tests, and linear regression 
Injury Prevention  1998;4(1):52-53.
PMCID: PMC1730336  PMID: 9595333
15.  Preoperative drug dispensing as predictor of surgical site infection. 
Emerging Infectious Diseases  2001;7(1):57-65.
The system used by the National Nosocomial Infection Surveillance (NNIS) program to measure risk of surgical site infection uses a score of 3 on the American Society of Anesthesiologists (ASA)-physical status scale as a measure of underlying illness. The chronic disease score measures health status as a function of age, sex, and 29 chronic diseases, inferred from dispensing of prescription drugs. We studied the relationship between the chronic disease score and surgical site infection and whether the score can supplement the NNIS risk index. In a retrospective comparison of 191 patients with surgical site infection and 378 uninfected controls, the chronic disease score and ASA score were highly correlated. The chronic disease score improved prediction of infection by the NNIS risk index and augmented the ASA score for risk adjustment.
PMCID: PMC2631693  PMID: 11266295
16.  Logistic regression and odds ratios. 
Injury Prevention  1997;3(4):294.
PMCID: PMC1067857  PMID: 9493627
18.  Statistical commentary. 
Injury Prevention  1997;3(2):87-88.
PMCID: PMC1067785  PMID: 9213151
19.  Using automated pharmacy records to assess the management of tuberculosis. 
Emerging Infectious Diseases  1999;5(6):788-791.
We used automated pharmacy dispensing data to characterize tuberculosis (TB) management for 45 health maintenance organization (HMO) members. Pharmacy records distinguished patients treated in HMOs from those treated elsewhere. For cases treated in HMOs, they provided useful information about appropriateness of prescribed regimens and adherence to therapy.
PMCID: PMC2640807  PMID: 10603212
20.  Supplementing tuberculosis surveillance with automated data from health maintenance organizations. 
Emerging Infectious Diseases  1999;5(6):779-787.
Data collected by health maintenance organizations (HMOs), which provide care for an increasing number of persons with tuberculosis (TB), may be used to complement traditional TB surveillance. We evaluated the ability of HMO-based surveillance to contribute to overall TB reporting through the use of routinely collected automated data for approximately 350,000 HMO members. During approximately 1.5 million person-years, 45 incident cases were identified in either HMO or public health department records. Eight (18%) confirmed cases had not been identified by the public health department. The most useful screening criterion (sensitivity of 89% and predictive value positive of 30%) was dispensing of two or more TB drugs. Pharmacy dispensing information routinely collected by many HMOs appears to be a useful adjunct to traditional TB surveillance, particularly for identifying cases without positive microbiologic results that may be missed by traditional public health surveillance methods.
PMCID: PMC2640806  PMID: 10603211
22.  Cytidine deaminase activity, C reactive protein, histidine, and erythrocyte sedimentation rate as measures of disease activity in psoriatic arthritis. 
Annals of the Rheumatic Diseases  1991;50(6):362-365.
Cytidine deaminase activity, C reactive protein, histidine, and erythrocyte sedimentation rate were measured in 36 subjects with psoriatic arthritis of varying disease duration and severity. Although cytidine deaminase activity may provide an integrated measure of synovial inflammation in rheumatoid arthritis, neutrophil accumulation in psoriatic plaques compromises this measure in psoriatic arthritis. Low histidine concentrations confirm that this amino acid provides a non-specific index of synovial inflammation. In psoriatic arthritis high C reactive protein concentrations seem to be associated with extensive joint destruction. In this study the erythrocyte sedimentation rate was found to be the best laboratory guide to clinical disease activity in psoriatic arthritis.
PMCID: PMC1004437  PMID: 2059079
23.  Fifteen-year experience with bloodstream isolates of coagulase-negative staphylococci in neonatal intensive care. 
Journal of Clinical Microbiology  1988;26(4):713-718.
Investigators worldwide, as well as the neonatologists and infection control team at our hospital, have reported that the incidence of coagulase-negative staphylococcal bacteremia in critically ill neonates has increased dramatically in recent years. To investigate these claims, we examined the results of all blood cultures obtained from 1970 to 1984 in our neonatal intensive care unit. Throughout this study period, coagulase-negative staphylococci were prominent blood culture isolates (crude overall incidence of 4.4 positive bacteremia workups per 100 neonates admitted; range, 2.5 to 6.7), representing 26.3 to 69.6% of all positive cultures. There was no significant increase in incidence over time by analysis of linear trend. Detailed analysis of data from 1976 and 1982 (two selected years for which complete information concerning culturing practices and patient characteristics was available) revealed that these observations were not explained by changes in the frequency of blood culturing. In both 1976 and 1982, the probability that a blood culture would grow coagulase-negative staphylococci increased steadily from 2 to 3% shortly after admission to reach a level of about 12% in week 3 of hospitalization, before declining to an intermediate level thereafter. This pattern is more consistent with nosocomial bacteremia than with contamination of blood cultures. Contrary to clinical reports, coagulase-negative staphylococci have been the principal pathogens isolated from blood cultures in our neonatal intensive care unit since at least 1970, with no measurable increase over the subsequent 14 years.
PMCID: PMC266424  PMID: 3366867
24.  Moxalactam therapy of infections caused by cephalothin-resistant bacteria: influence of serum inhibitory activity on clinical response and acquisition of antibiotic resistance during therapy. 
Thirty patients infected predominantly by Serratia marcescens and Pseudomonas aeruginosa were treated in an open trial with moxalactam, a broad-spectrum beta-lactam antibiotic. Twenty-three (76%) had a satisfactory microbiological or clinical response. Among 25 patients for whom serum inhibitory concentrations were measured, those with favorable microbiological responses had significantly higher values than those with poor responses (reciprocal geometric mean concentrations, 49 versus 4.9; P less than 0.01). A serum inhibitory concentration of greater than 1:8 correlated significantly with a favorable outcome (17 of 18 versus 2 of 7 responses; P less than 0.01). Although the overall clinical efficacy of moxalactam was good, resistant organisms of species identical to those of the original infecting isolates were recovered during therapy in seven cases, including five caused by Pseudomonas organisms and two caused by Serratia organisms.
PMCID: PMC181699  PMID: 6458233
25.  Thoughts on teaching medicine. 
British Medical Journal  1965;2(5461):551-552.
PMCID: PMC1845959  PMID: 5826899

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