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Biomedical subjects

David Anderson

Publications and source records attributed to David Anderson.

At least 55 records · Page 3Linked to original sources

A systematic review of economic analyses of low-molecular-weight heparin for the treatment of venous thromboembolism.

INTRODUCTION: Public concerns about the increase in health care expenditure have prompted investigators to analyze the costs and benefits of health care interventions. We conducted a systematic review of economic analyses of venous thromboembolism treatment focusing on studies evaluating low-molecular-weight heparin. MATERIALS AND METHODS: We identified studies by a MEDLINE search and a review of bibliographies of retrieved articles. From each eligible study, we extracted data on the study characteristics, the effectiveness, and the cost of managing the venous thromboembolism with respect to treatment. We critically appraised the studies according to the framework from the Users' Guides to the Medical Literature XIII: How to Use an Article on Economic Analysis of Clinical Practice. RESULTS: Six of these eight economic analyses of venous thromboembolism treatment that met the inclusion criteria for this review showed that low-molecular-weight heparin is associated with less recurrent venous thromboembolism and is less costly than treatment with unfractionated heparin. Although discrete recurrent venous thromboembolism event rates were not included in the seventh study, these investigators concluded that the cost of low-molecular-weight heparin for the treatment of venous thromboembolism treatment was offset by the savings associated with fewer hospital admissions when low-molecular-weight heparin was used. In the eighth study, although the cost of treatment with low-molecular-weight heparin was higher than treatment with unfractionated heparin, the investigators concluded that low-molecular-weight heparin is cost-effective for inpatient management. CONCLUSIONS: Low-molecular-weight heparin treatment may confer economic advantages over unfractionated heparin therapy because it does not require anticoagulant monitoring and it facilitates outpatient therapy.

Anticoagulants↗

Mediastinal haemangiomas in children.

A 5-month-old girl presented with upper airway obstruction and was found to have a mediastinal mass compressing the trachea. She successfully underwent resection of this mass, later confirmed to be a juvenile haemangioma. This case highlights mediastinal haemangiomas in the paediatric population as a diagnostic and therapeutic challenge, and the importance of a multidisciplinary approach in the management of such patients.

Cough↗

Multigene DNA prime-boost vaccines for SHIV89.6P.

We assessed four prime-boost vaccine regimens with a Gene Gun component for SHIV89.6P in Macaca nemestrina. A dosing experiment using beta-galactosidase plasmid showed that 30 or 45 shots per dose elicited higher titer antibody than smaller doses. For SHIV89.6P, we administered a six-plasmid vaccine capable of producing non-infectious virions in vivo in combination with either vaccinia recombinants or inactivated virus. DNA prime/vaccinia boost, or the reverse, elicited strong immune responses. The SHIV89.6P challenge virus was grown in M. nemestrina peripheral blood mononuclear cells and titered in vivo intrarectally. As has been observed for SHIV89.6P in M. mulatta, the infected M. nemestrina experienced rapid and severe loss of circulating CD4+ T cells. Vaccinated macaques were challenged three weeks after the last boost. DNA prime/vaccina boost or vaccina prime/DNA boost protected 11/12 animals from acute CD4+ T cell depletion and disease, while other regimens were not effective.

AIDS Vaccines↗

Inhibition of annexin V binding to cardiolipin and thrombin generation in an unselected population with venous thrombosis.

OBJECTIVE: To examine the effect on annexin V binding to cardiolipin (CL) and in vitro thrombin generation by plasma samples from an unselected population of patients with confirmed venous thrombosis and matched controls. The prevalence of autoimmune antiphospholipid antibodies (aPL) was also determined. METHODS: A total of 111 patients who presented to a single emergency room with symptoms suggestive of venous thromboembolic (VTE) disease were studied. In 34 patients the diagnosis of lower limb deep venous thrombosis (DVT) and/or pulmonary embolus (PE) was confirmed (VTE+ group). In the remaining 77 patients the diagnostic workup was negative (VTE- group). Plasma samples were collected prior to the initiation of anticoagulation and examined for IgG anticardiolipin (aCL), IgG anti-beta2-glycoprotein I (GPI), and IgG anti-prothrombin (aPT antibodies) by ELISA. In addition, the effect of individual patient and control plasma samples on annexin V binding to CL and on in vitro thrombin generation was determined by a competitive ELISA and a chromogenic assay, respectively. RESULTS: The prevalence and levels of IgG aCL, anti-beta2-GPI, and aPT antibodies were similar in the VTE+ and VTE- groups. However, plasma samples from the VTE+ group caused a significant inhibition of in vitro thrombin generation (mean +/- SD Z score: -0.66 +/- 0.97 vs 0.26 +/- 1.46; p < 0.001) and a concurrent but less impressive inhibition of annexin V binding to CL (mean +/- SD Z score: -2.53 +/- 1.44 vs -2.05 +/- 1.61; p = 0.123). Upon analyzing a panel of clinical and laboratory variables, only age and inhibition of thrombin generation were significantly associated with VTE disease. CONCLUSION: Our findings suggest that subtle abnormalities in annexin V physiology may contribute to the procoagulant state in patients with idiopathic venous thrombosis.

Annexin A5↗

Stroke prevention in hospitalized patients with atrial fibrillation: a population-based study.

BACKGROUND: Oral anticoagulants reduce the incidence of stroke by 68%, yet suboptimal use has been documented in surveys of patients with atrial fibrillation. The present study examined current patterns of anticoagulant use for patients hospitalized with atrial fibrillation across an entire health care system. METHODS: Improving Cardiovascular Outcomes in Nova Scotia (ICONS) is a prospective cohort study involving all patients hospitalized in Nova Scotia with atrial fibrillation, among other conditions. Consecutive inpatients with atrial fibrillation from October 15, 1997 to October 14, 1998 were studied. Detailed demographic and clinical data were collected and the proportion of patients using antithrombotic therapy was tabulated by risk category. Multivariate logistic regression was used to assess the relationship of various demographic and clinical factors with the use of antithrombotic agents. RESULTS: There were 2202 patients hospitalized with atrial fibrillation; 644 admitted specifically for this condition. Only 21% of patients admitted with atrial fibrillation were on warfarin sodium at admission and this increased by time of discharge. Diabetes was negatively correlated with warfarin sodium use. Histories of prosthetic valve replacement, stroke/transient ischemic attack, and heart failure were positively associated with anticoagulant use on admission. Patients with prosthetic valve replacement, heart failure, or hyperlipidemia were most likely to receive anticoagulants at discharge. CONCLUSION: Antithrombotic agents remain underused by patients with atrial fibrillation. While higher risk patients are generally targeted, this is not invariably the case; thus, diabetics remain under treated. Further work is needed to explain such anomalous practice and promote optimal antithrombotic therapy use.

Aged↗

Hepatic drug targeting: phase I evaluation of polymer-bound doxorubicin.

PURPOSE: Preclinical studies have shown good anticancer activity following targeting of a polymer bearing doxorubicin with galactosamine (PK2) to the liver. The present phase I study was devised to determine the toxicity, pharmacokinetic profile, and targeting capability of PK2. PATIENTS AND METHODS: Doxorubicin was linked via a lysosomally degradable tetrapeptide sequence to N-(2-hydroxypropyl)methacrylamide copolymers bearing galactosamine. Targeting, toxicity, and efficacy were evaluated in 31 patients with primary (n = 25) or metastatic (n = 6) liver cancer. Body distribution of the radiolabelled polymer conjugate was assessed using gamma-camera imaging and single-photon emission computed tomography. RESULTS: The polymer was administered by intravenous (i.v.) infusion over 1 hour, repeated every 3 weeks. Dose escalation proceeded from 20 to 160 mg/m(2) (doxorubicin equivalents), the maximum-tolerated dose, which was associated with severe fatigue, grade 4 neutropenia, and grade 3 mucositis. Twenty-four hours after administration, 16.9% +/- 3.9% of the administered dose of doxorubicin targeted to the liver and 3.3% +/- 5.6% of dose was delivered to tumor. Doxorubicin-polymer conjugate without galactosamine showed no targeting. Three hepatoma patients showed partial responses, with one in continuing partial remission 47 months after therapy. CONCLUSION: The recommended PK2 dose is 120 mg/m(2), administered every 3 weeks by IV infusion. Liver-specific doxorubicin delivery is achievable using galactosamine-modified polymers, and targeting is also seen in primary hepatocellular tumors.

Antineoplastic Agents↗

Views of elderly patients on cardiopulmonary resuscitation before and after treatment for depression.

OBJECTIVE: To investigate elderly patients decision to accept cardiopulmonary resuscitation (CPR) before and after treatment for depression. METHODS: A Prospective cohort study set within a specialist psychiatrist hospital for the elderly. The subjects were 50 consecutively admitted day and in-patients with depression. Changes in the acceptability of CPR between baseline and end of treatment for depression together with patient characteristics were measured and compared. RESULTS: 49 patients completed the study; all but one of the 17 patients who initially declined CPR accepted once recovered and none who initially accepted later changed their minds (p=0.0001. CONCLUSIONS: The study demonstrates that depressed elderly people frequently decline CPR but accept after recovery from depression. The presence of depression should be specifically considered if an elderly person unexpectedly declines CPR.

Aged↗

Domiciliary clinics II: a cost minimisation analysis.

OBJECTIVES: We compare the cost of assessing new referrals to an old age psychiatry service at the patient's home or a hospital-based clinic. METHOD: An old age psychiatry service in Liverpool where routine referrals were assessed at home (domiciliary clinic) was compared to an adjacent service which assessed people in an outpatient clinic. Activity levels for four years of the service were collected and analysed. A cost-minimization analysis was done using an algorithm which allowed all direct costs to the service to be taken into account. A sensitivity analysis changed key values of the algorithm allowing their relative contribution to be considered. RESULT: The domiciliary clinic was marginally cheaper than outpatient assessment (48 pounds sterling compared to 50 pounds sterling per successful assessment). The most important variables in determining the cost effectiveness of the service were non-attendance rates, the grade of doctor seeing the patient and the time spent traveling for the home assessment. CONCLUSIONS: Domiciliary initial assessments were comparable in cost to clinic assessments in this study but in other situations the cost will vary, depending on the key local variables.

Aged↗

Artificial life and the Chinese room argument.

"Strong artificial life" refers to the thesis that a sufficiently sophisticated computer simulation of a life form is a life form in its own right. Can John Searle's Chinese room argument [12]-originally intended by him to show that the thesis he dubs "strong AI" is false-be deployed against strong ALife? We have often encountered the suggestion that it can be (even in print; see Harnad [8]). We do our best to transfer the argument from the domain of AI to that of ALife. We do so in order to show once and for all that the Chinese room argument proves nothing about ALife. There may indeed be powerful philosophical objections to the thesis of strong ALife, but the Chinese room argument is not among them.

Artificial Intelligence↗

Factors affecting outcome following transplantation of ex vivo expanded limbal epithelium on amniotic membrane for total limbal deficiency in rabbits.

PURPOSE: To determine factors affecting the outcome of corneal surface reconstruction in rabbits with total limbal stem cell deficiency (LSCD), by using autologous limbal epithelial stem cells (LSC) ex vivo, expanded on rabbit amniotic membrane (AM). METHODS: Left eyes of 52 rabbits were rendered totally limbal stem cell deficient by n-heptanol debridement of the entire corneal epithelium followed by surgical removal of 360 degrees of limbal rim. After cytologic verification of LSCD, the fibrovascular pannus of each cornea was removed. Group I (n = 10) received a rabbit AM transplant, whereas groups II, III, and IV (n = 42) underwent transplantation of LSCs cultured on rabbit AM (LSC-AM graft) derived from a small limbal biopsy specimen from the right eye. Clinical outcome was graded as a success if a smooth, avascular corneal surface was restored, a partial success if more than two quadrants of corneal surface were smooth, or a failure if the corneal surface was revascularized and irregular. RESULTS: A long-term follow-up of more than 1 year was achieved. Compared with the 100% failure rate in group I, inclusion of expanded LSCs resulted in variable success rates in groups II, III, and IV (all P < 0.001). Kaplan-Meier survival analysis showed that different suturing techniques, subconjunctival injection of long-acting steroid, and tarsorrhaphy used in groups II (n = 17) and III (n = 13) did not significantly alter the outcome (P = 0.89). However, the use of a larger graft and human AM as a temporary patch with the explant retained for 1 week in group IV (n = 12) significantly improved the success rate to 83% (P = 0.002). Among eyes showing clinical failure, there was a significant correlation between the logarithm of the first day when an epithelial defect was noted and the time of graft failure (r(2) = 0.60, P < 0.001). Furthermore, the presence of severe lid deformity was borderline significant when correlated with failure cases in all four groups (P = 0.069). CONCLUSIONS: Ex vivo expansion of LSCs can be achieved by using rabbit AM culture. Such expanded LSCs can successfully reconstruct corneal surfaces affected by total LSCD. This animal model is useful to investigate culturing variables affecting epithelial stemness so that surgical reconstruction of corneas with total LSCD can be successfully performed. Furthermore, this model can be used to test the feasibility of gene therapies targeting LSCD in the future.

Amnion↗

Atrial septal defect with failure to thrive in infancy: hidden pulmonary vascular disease?

Atrial septal defects are usually asymptomatic, and are closed surgically or by a catheter implanted device in preschool age children. Rarely, they may cause symptoms in infancy, and management at this age is debated. We report our experience of six infants who underwent surgical closure, with variable outcomes. Five of these had significant extracardiac pathology. Our data suggest the need to exclude other causes of symptoms, both cardiac and non-cardiac. The question should be asked as to whether surgery is of benefit in these children, and particularly whether they may have underlying primary pulmonary vascular disease.

Failure to Thrive↗

Multimodel ranking and inference in ground water modeling.

Uncertainty of hydrogeologic conditions makes it important to consider alternative plausible models in an effort to evaluate the character of a ground water system, maintain parsimony, and make predictions with reasonable definition of their uncertainty. When multiple models are considered, data collection and analysis focus on evaluation of which model(s) is(are) most supported by the data. Generally, more than one model provides a similar acceptable fit to the observations; thus, inference should be made from multiple models. Kullback-Leibler (K-L) information provides a rigorous foundation for model inference that is simple to compute, is easy to interpret, selects parsimonious models, and provides a more realistic measure of precision than evaluation of any one model or evaluation based on other commonly referenced model selection criteria. These alternative criteria strive to identify the true (or quasi-true) model, assume it is represented by one of the models in the set, and given their preference for parsimony regardless of the available number of observations the selected model may be underfit. This is in sharp contrast to the K-L information approach, where models are considered to be approximations to reality, and it is expected that more details of the system will be revealed when more data are available. We provide a simple, computer-generated example to illustrate the procedure for multimodel inference based on K-L information and present arguments, based on statistical underpinnings that have been overlooked with time, that its theoretical basis renders it preferable to other approaches.

Evaluation Studies as Topic↗

Placebo practice trials: a tool to assess and improve adherence readiness.

PURPOSE: Antiretroviral therapy is being increasingly delayed until later stages of illness. Therefore, prior to prescribing HAART, providers are emphasizing the need for patients to be ready to adhere well to the treatment regimen. Unfortunately, providers are no better than chance at predicting a patient's adherence, and there are no established methods for accurately assessing a patient's adherence readiness. This pilot study assessed the utility of a series of up to five 1-week placebo practice trials accompanied by adherence counseling as a clinical tool to both assess and improve adherence readiness. METHOD: Participants were not prescribed treatment until they demonstrated readiness, which was defined as 90+% adherence during a single practice trial. Once HAART was initiated, adherence to one selected antiretroviral was monitored for 4 weeks. Electronic monitoring caps were used to measure adherence. RESULTS: Twenty men enrolled in the study at two HIV outpatient clinics in Southern California. Mean age was 33, 50% were non-White, 35% were employed, 30% had not completed high school, 15% were Spanish monolingual, and 30% had unstable housing. Nine participants achieved 90+% adherence in the first practice trial, with an additional 8 participants demonstrating readiness after two to four practice trials; two participants withdrew from the study because of intolerance of the restrictions related to the use of the caps; and one participant was removed from the study after no effort was given during two practice trials. Of the 17 participants who completed the program and demonstrated adherence readiness, 15 started on an antiretroviral regimen and 2 decided to defer treatment indefinitely. Of the 15 who started therapy, 13 (87%) achieved 90+% adherence during the first month of antiretroviral therapy. The sample's mean adherence during the first 4 weeks of treatment was 93% (SD = 13). CONCLUSION: These results suggest that once a patient is able to adhere well to a 1-week practice trial they are likely to adhere equally well to HAART. A larger controlled study is needed to further assess the effectiveness of practice trials as a clinical tool for both assessing and improving adherence readiness.

Adult↗

The use of general anesthesia to facilitate dental treatment.

General anesthesia can help the dental professional provide treatment to individuals who otherwise would be unable to receive dental care. State-mandated training, current anesthesia techniques, and adequate planning by the dentist make general anesthesia safe and effective in the private dental office. This article discusses the multiple benefits general anesthesia offers both the dentist and the patient. Suggestions are presented to facilitate the accessibility and utilization of general anesthesia for routine office dental care.

Anesthesia Recovery Period↗