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Biomedical subjects

Richard Cook

Publications and source records attributed to Richard Cook.

11 recordsLinked to original sources
PubMed2006

Inhalation exposure and risk from mobile source air toxics in future years.

Modeling of inhalation exposure and risks resulting from exposure to mobile source air toxics can be used to evaluate impacts of reductions from control programs on overall risk, as well as changes in relative contributions of different source sectors to risk, changes in contributions of different pollutants to overall risk, and changes in geographic distributions of risk. Such analysis is useful in setting regulatory priorities, and informing the decision-making process. In this paper, we have conducted national-scale air quality, exposure, and risk modeling for the US in the years 2015, 2020, and 2030, using similar tools and methods as the 1999 National-Scale Air Toxics Assessment. Our results suggest that US Environmental Protection Agency emission control programs will substantially reduce average inhalation cancer risks and potential noncancer health risks from exposure to mobile source air toxics. However, cancer risk and noncancer hazard due to inhalation of air toxics will continue to be a public health concern.

Air Pollutants↗
PubMed2005

Predictive value of bone resorption and formation markers in cancer patients with bone metastases receiving the bisphosphonate zoledronic acid.

PURPOSE: Three large, randomized trials of patients with bone metastases recently demonstrated that zoledronic acid reduces the risk of skeletal-related events. These trials provide an opportunity for investigating the correlation between bone metabolism and clinical outcome during bisphosphonate therapy. PATIENTS AND METHODS: Urinary measurements of N-telopeptide (Ntx) and serum bone alkaline phosphatase (BAP) were obtained in 1,824 bisphosphonate-treated patients-1,462 with zoledronic acid (breast, 490; prostate, 411; myeloma, 210; non-small-cell lung, 183; other, 168) and 362 with pamidronate (breast, 254; myeloma, 108). This exploratory cohort analysis grouped patients by baseline and most recent levels of Ntx as low (< 50 nmol/mmol creatinine), moderate (50 to 99 nmol/mmol creatinine), or high (> or = 100 nmol/mmol creatinine), and BAP as low (< 146 U/L) or high (> or = 146 U/L). The relative risks for negative clinical outcomes were estimated for each group using multiple-event and Cox regression models with time-varying covariates. RESULTS: Patients with high and moderate Ntx levels had 2-fold increases in their risk of skeletal complications and disease progression compared with patients with low Ntx levels (P < .001 for all). High Ntx levels in each solid tumor category were associated with a 4- to 6-fold increased risk of death on study, and moderate Ntx levels a 2- to 4-fold increased risk compared with low Ntx levels (P < .001 for all). Bone alkaline phosphatase also showed some correlation with risk of negative clinical outcomes. CONCLUSION: The bone resorption marker Ntx provides valuable prognostic information in patients with bone metastases receiving bisphosphonates.

Adult↗
PubMed2005

Natural history of rising serum prostate-specific antigen in men with castrate nonmetastatic prostate cancer.

PURPOSE: To describe the natural history of nonmetastatic prostate cancer and rising prostate-specific antigen (PSA) despite androgen deprivation therapy. PATIENTS AND METHODS: The 201 patients in this report were the placebo control group from an aborted randomized controlled trial to evaluate the effects of zoledronic acid on time to first bone metastasis in men with prostate cancer, no bone metastases, and rising PSA despite androgen deprivation therapy. Relationships between baseline covariates and clinical outcomes were assessed by Cox proportional hazard analyses. Covariates in the model were baseline PSA, Gleason sum, history of bilateral orchiectomies, regional lymph node metastases at diagnosis, prior prostatectomy, time from androgen deprivation therapy to random assignment, time from diagnosis to random assignment, and PSA velocity. RESULTS: At 2 years, 33% of patients had developed bone metastases. Median bone metastasis-free survival was 30 months. Median time to first bone metastases and overall survival were not reached. Baseline PSA level greater than 10 ng/mL (relative risk, 3.18; 95% CI, 1.74 to 5.80; P < .001) and PSA velocity (4.34 for each 0.01 increase in PSA velocity; 95% CI, 2.30 to 8.21; P < .001) independently predicted shorter time to first bone metastasis. Baseline PSA and PSA velocity also independently predicted overall survival and metastasis-free survival. Other covariates did not consistently predict clinical outcomes. CONCLUSION: Men with nonmetastatic prostate cancer and rising PSA despite androgen deprivation therapy have a relatively indolent natural history. Baseline PSA and PSA velocity independently predict time to first bone metastasis and survival.

Aged↗
PubMed2005

Mapping cognitive work: the way out of healthcare IT system failures.

The failure of automation to improve clinical performance is likely rooted in the design concepts on which IT systems are based. Current systems provide clinicians with specific direction about how to care for individual patients. This is much like the specific, detailed, complicated, and narrow trip route driving directions that can be obtained from various web sites. Daily healthcare work rarely has the certainty that makes such directions useful. Rather than directions, useful healthcare automation is likely to have characteristics of a map. Clinicians could use its depictions of available routes, obstacles, and distances between the current and goal locations in order to choose routes and to track progress toward goals. Such representations are likely to be quite different than those currently incorporated in healthcare automation. We demonstrate the concept of creating maps and using constraints as the basis for the design of healthcare automation.

Cognition↗
PubMed2004

Prediction of falls using a risk assessment tool in the acute care setting.

BACKGROUND: The British STRATIFY tool was previously developed to predict falls in hospital. Although the tool has several strengths, certain limitations exist which may not allow generalizability to a Canadian setting. Thus, we tested the STRATIFY tool with some modification and re-weighting of items in Canadian hospitals. METHODS: This was a prospective validation cohort study in four acute care medical units of two teaching hospitals in Hamilton, Ontario. In total, 620 patients over the age of 65 years admitted during a 6-month period. Five patient characteristics found to be risk factors for falls in the British STRATIFY study were tested for predictive validity. The characteristics included history of falls, mental impairment, visual impairment, toileting, and dependency in transfers and mobility. Multivariate logistic regression was used to obtain optimal weights for the construction of a risk score. A receiver-operating characteristic curve was generated to show sensitivities and specificities for predicting falls based on different threshold scores for considering patients at high risk. RESULTS: Inter-rater reliability for the weighted risk score indicated very good agreement (inter-class correlation coefficient = 0.78). History of falls, mental impairment, toileting difficulties, and dependency in transfer / mobility significantly predicted fallers. In the multivariate model, mental status was a significant predictor (P < 0.001) while history of falls and transfer / mobility difficulties approached significance (P = 0.089 and P = 0.077 respectively). The logistic regression model led to weights for a risk score on a 30-point scale. A risk score of 9 or more gave a sensitivity of 91% and specificity of 60% for predicting who would fall. CONCLUSION: Good predictive validity for identifying fallers was achieved in a Canadian setting using a simple-to-obtain risk score that can easily be incorporated into practice.

Accidental Falls↗
PubMed2004

Stepped-care approach to treating MS: a managed care treatment algorithm.

OBJECTIVE: To introduce a model treatment algorithm for use in the managed care setting as a strategy to provide ongoing disease management and long-term care for patients with multiple sclerosis (MS), with the goal of delaying disease progression and the associated disability and cognitive dysfunction. SUMMARY: MS is a chronic inflammatory disorder of the central nervous system that is associated with progressive disability and cognitive dysfunction. Currently, management of MS involves planning an effective long-term treatment strategy that can delay the progression of the disease. This article reviews a typical stepped-care approach to treating MS that is based on the concept of a platform drug, which is an agent that provides baseline immunomodulatory action throughout the course of the disease. Considerations for selecting a platform therapy include the effect on the full spectrum of MS (disability, relapses, lesion load, and atrophy as well as patient compliance and the potential impact of neutralizing antibodies [NAbs]). Currently, 4 first-line therapies are approved for relapsing MS: the 3 interferon beta (IFNbeta) products and glatiramer acetate. Of these, the IFNbetas are generally recommended as platform therapy because all have shown significant effects on relapses, magnetic resonance imaging parameters of the disease, and because intramuscular (i.m.) IFNbeta-1a (Avonex) and subcutaneous (s.c.) IFNbeta-1a (Rebif) have been shown to slow the progression of sustained disability. Patients being treated with IFNbetas can develop NAbs to the drug, which can lead to a loss of efficacy and subsequent occurrence of breakthrough disease. The 3 different formulations of IFNbeta are associated with a varying incidence of NAbs (i.m. IFNbeta-1a, 5%; s.c. IFNbeta-1a, 24%; IFNbeta-1b [Betaseron], 45%). Antibodies also form against glatiramer acetate, although their clinical significance needs to be elucidated. As the disease progresses or has periods of aggressive activity, the stepped-care approach is to add other agents onto the platform therapy to improve control of the disease. CONCLUSION: Stepped care, as outlined in this model treatment algorithm for the managed care setting, is an effective method to achieve the fundamental goal of MS treatment, that is, to delay disease progression and the associated disability and cognitive impairment.

Adjuvants, Immunologic↗
PubMed2002

Efficacy of bisphosphonates in the management of skeletal complications of bone metastases and selection of clinical endpoints.

Bisphosphonates are the current standard of palliative care for patients with bone lesions from breast cancer and multiple myeloma. This article discusses the selection of endpoints and statistical methods used to assess clinical efficacy of bisphosphonate therapies in patients with bone metastases. Recent studies of pamidronate and zoledronic acid have set the standards for the design and conduct of multicenter, randomized, placebo-controlled trials to assess the clinical benefit of bisphosphonates in patients with bone metastases. Studies of zoledronic acid have demonstrated objective, significant, and enduring benefits in patients with a broad range of primary cancers, including prostate cancer, using robust clinical endpoints. Other bisphosphonates, including clodronate, have been investigated for the treatment of bone metastases, but these studies have been relatively small. This review first considers issues of trial design and analysis, with particular emphasis on the statistical requirements for the rigorous analysis of multiple events occurring in the same patient, and then reviews the results of bisphosphonate trials in patients with breast or prostate cancers metastatic to bone in the light of these statistical considerations.

Bone Neoplasms↗
PubMedDate not supplied

Image-space visibility ordering for cell projection volume rendering of unstructured data.

Projection methods for volume rendering unstructured data work by projecting, in visibility order, the polyhedral cells of the mesh onto the image plane, and incrementally compositing each cell's color and opacity into the final image. Normally, such methods require an algorithm to determine a visibility order of the cells. The Meshed Polyhedra Visibility Order (MPVO) algorithm can provide such an order for convex meshes by considering the implications of local ordering relations between cells sharing a common face. However, in nonconvex meshes, one must also consider ordering relations along viewing rays which cross empty space between cells. In order to include these relations, the algorithm described in this paper, the scanning exact meshed polyhedra visibility ordering (SXMPVO) algorithm, scan-converts the exterior faces of the mesh and saves the ray-face intersections in an A-Buffer data structure which is then used for retrieving the extra ordering relations. The image which SXMPVO produces is the same as would be produced by ordering the cells exactly, even though SXMPVO does not compute an exact visibility ordering. This is because the image resolution used for computing the visibility ordering relations is the same as that which is used for the actual volume rendering and we choose our A-Buffer rays at the same sample points that are used to establish a polygon's pixel coverage during hardware scan conversion. Thus, the algorithm is image-space correct. The SXMPVO algorithm has several desirable features; among them are speed, simplicity of implementation, and no extra (i.e., with respect to MPVO) preprocessing.

Journal Article↗