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Biomedical subjects

D Cook

Publications and source records attributed to D Cook.

At least 19 recordsLinked to original sources

Minimizing errors of omission: behavioural reenforcement of heparin to avert venous emboli: the BEHAVE study.

OBJECTIVE: To improve patient safety by increasing heparin thromboprophylaxis for medical-surgical intensive care unit patients using a multiple-method approach to evidence-based guideline development and implementation. DESIGN: Prospective longitudinal observational study. SETTING: Medical-surgical intensive care unit. PARTICIPANTS: Multidisciplinary clinicians caring for critically ill patients in a 15-bed medical-surgical closed intensive care unit. INTERVENTIONS: Phase 1 was a 3-month baseline period during which we documented anticoagulation and mechanical thromboprophylaxis. Phase 2 was a 1-yr period in which we implemented a thromboprophylaxis guideline using a) interactive multidisciplinary educational in-services; b) verbal reminders to the intensive care unit team; c) computerized daily nurse recording of thromboprophylaxis; d) weekly graphic feedback to individual intensivists on guideline adherence; and e) publicly displayed graphic feedback on group performance. Phase 3 was a 3-month follow-up period 10 months later, during which we documented thromboprophylaxis. Computerized daily nurse recording of thromboprophylaxis continued in this period. MEASUREMENTS AND MAIN RESULTS: Intensive care unit and hospital mortality rates were similar across phases, although patients in phase 2 had higher Acute Physiology and Chronic Health Evaluation II scores than patients in phases 1 and 3. The proportion (median % [interquartile range]) of intensive care unit patient-days of heparin thromboprophylaxis in phases 1, 2, and 3 was 60.0 (0, 100), 90.9 (50, 100), and 100.0 (60, 100), respectively (p=.01). The proportion (median % [interquartile range]) of days during which heparin thromboprophylaxis was omitted in error in phases 1, 2, and 3 was 20 (0, 53.8), 0 (0, 6.3), and 0 (0, 0), respectively (p<.001). CONCLUSIONS: After development and implementation of an evidence-based thromboprophylaxis guideline, we found significantly more patients receiving heparin thromboprophylaxis. Guideline adherence was maintained 1 yr later. Further research is needed on which are the most effective strategies to implement patient safety initiatives in the intensive care unit.

Aged↗

Decision tools for life support: a review and policy analysis.

OBJECTIVE: To identify, describe, and compare published documents intended to guide decisions about the administration, withholding, or withdrawal of life support in critical care. DESIGN: Review article. SETTING AND SOURCES: Publicly available, English-language guidelines or decision tools for life support, identified through systematic literature search. MEASUREMENTS AND MAIN RESULTS: Forty-nine documents were included and coded for authorship, source, development methodology, format, and positions taken on 12 common life-support issues. Sources were independent academics (n=21, 43%), professional organizations (n=19, 44%), and provider organizations. Eighteen documents (37%) described no development method. Twenty-three (47%) were produced collectively (e.g., by committees or consensus conference), 7 (14%) mentioned a literature review, and 2 (4%) were based upon the author's professional experience. Tools differed in format and focus; we characterize three types as decision schemas (involving clinical practice algorithms; n=7, 14%), decision guides (reviewing legal or professional positions; n=29, 59%), and decision counsels (more discursive and focusing typically on ethical issues; n=13, 27%). Tools addressed 12 common life-support issues: advance directives (67%), resource considerations (51%), ICU discharge criteria (27%), ICU admission criteria (16%), whether withholding differs from withdrawing life support (59%), whether nutrition and hydration decisions are different from decisions about other types of life support (61%), euthanasia (49%), double effect (47%), brain death (35%), special considerations for patients in a persistent vegetative state (51%), potential organ donors (12%), and pregnant patients (10%). Positions on these key life-support issues varied. CONCLUSIONS: Published tools for guiding life-support decisions vary widely in their genesis, authorship, format, focus, and practicality. They also differ in their attention to, and positions on, key life-support dilemmas. Future research on decision tools should focus on how users interpret and apply the messages in these tools and their impacts on practice, quality of care, participant experiences, and outcomes.

Decision Support Techniques↗

Rain, winds and haze during the Huygens probe's descent to Titan's surface.

The irreversible conversion of methane into higher hydrocarbons in Titan's stratosphere implies a surface or subsurface methane reservoir. Recent measurements from the cameras aboard the Cassini orbiter fail to see a global reservoir, but the methane and smog in Titan's atmosphere impedes the search for hydrocarbons on the surface. Here we report spectra and high-resolution images obtained by the Huygens Probe Descent Imager/Spectral Radiometer instrument in Titan's atmosphere. Although these images do not show liquid hydrocarbon pools on the surface, they do reveal the traces of once flowing liquid. Surprisingly like Earth, the brighter highland regions show complex systems draining into flat, dark lowlands. Images taken after landing are of a dry riverbed. The infrared reflectance spectrum measured for the surface is unlike any other in the Solar System; there is a red slope in the optical range that is consistent with an organic material such as tholins, and absorption from water ice is seen. However, a blue slope in the near-infrared suggests another, unknown constituent. The number density of haze particles increases by a factor of just a few from an altitude of 150 km to the surface, with no clear space below the tropopause. The methane relative humidity near the surface is 50 per cent.

Atmosphere↗

Upper limits on a stochastic background of gravitational waves.

The Laser Interferometer Gravitational-Wave Observatory has performed a third science run with much improved sensitivities of all three interferometers. We present an analysis of approximately 200 hours of data acquired during this run, used to search for a stochastic background of gravitational radiation. We place upper bounds on the energy density stored as gravitational radiation for three different spectral power laws. For the flat spectrum, our limit of omega0 < 8.4 x 10(-4) in the 69-156 Hz band is approximately 10(5) times lower than the previous result in this frequency range.

Journal Article↗

Limits on gravitational-wave emission from selected pulsars using LIGO data.

We place direct upper limits on the amplitude of gravitational waves from 28 isolated radio pulsars by a coherent multidetector analysis of the data collected during the second science run of the LIGO interferometric detectors. These are the first direct upper limits for 26 of the 28 pulsars. We use coordinated radio observations for the first time to build radio-guided phase templates for the expected gravitational-wave signals. The unprecedented sensitivity of the detectors allows us to set strain upper limits as low as a few times 10(-24). These strain limits translate into limits on the equatorial ellipticities of the pulsars, which are smaller than 10(-5) for the four closest pulsars.

Journal Article↗

CD8+ T-cell-depleted, matched unrelated donor, allogeneic bone marrow transplantation for advanced AML using busulfan-based preparative regimens.

The role of T-cell depletion (TCD) to prevent graft-versus-host disease (GVHD) after matched unrelated donor allogeneic bone marrow transplant (MUD BMT) remains undefined. Most studies employ total body irradiation and pan TCD. Between March 1993 and June 2002, we treated 33 relapsed acute myelogenous leukemia (AML) patients with busulfan-based preparative regimens and selective TCD. The preparative regimen consisted of busulfan 14 mg/kg, cyclophosphamide 120 mg/kg and VP-16 50 mg/kg in all but one patient who only received busulfan and cyclophosphamide. Donor marrow was depleted of CD8+ T cells by immunomagnetic bead separation. The patients were also treated with cyclosporine and methylprednisolone or FK-506 and mini-dose methotrexate. Four (15%) of 33 patients developed graft failure or rejection. However, three of these patients were serologically mismatched at HLA-Cw. Although 67% of evaluable patients developed acute GVHD, severe grade III-IV acute GVHD only developed in 19%. The severity of acute GVHD correlated with the degree of CD8+ TCD. Median relapse-free survival was 5 months among 20 patients treated with active AML, and 28 months among 13 patients treated in complete remission. Our results confirm that MUD BMT with CD8+ TCD for AML is a potentially curative treatment option.

Adult↗

Polymerase chain reaction aids in the diagnosis of an unusual case of Aspergillus niger endocarditis in a patient with acute myeloid leukaemia.

Endocarditis secondary to Aspergillus niger has not been described in a leukaemic patient. We describe a case of A. niger endocarditis in a patient with acute myeloid leukaemia and refractory fever. The microbiological cause of his endocarditis was initially misdiagnosed because he fulfilled the Duke criteria for enterococcal endocarditis. A polymerase chain reaction test utilizing pan-fungal primers detected a product from an Aspergillus sp. The DNA was subsequently sequenced and was found to have 100% homology with A. niger. A postmortem revealed fungal endocarditis secondary to disseminated aspergillosis, without evidence of bacterial endocarditis. The patient was found to have a lung aspergilloma that was possibly occupationally acquired, and may have been long standing.

Aspergillosis↗

Treatment options for microcystin toxins: similarities and differences between variants.

Over sixty variants of the blue-green algal toxin microcystin have been identified. The two microcystin variants LR and LA vary in only one amino group ie. arginine for microcystin LR and alanine for microcystin LA. In the literature to date, the general consensus has been that m-LR and m-LA should respond similarly to a range of water treatment processes. This is the case for ozonation and biodegradation by organisms colonising granular activated carbon filters; there is negligible difference in the response to these processes between the two variants. However, the adsorption of m-LR onto activated carbon is significantly higher than that of m-LA. This result is surprising as m-LA has a lower molecular weight, and is more hydrophobic, factors that would be expected to favour the adsorption of this compound over m-LR. This trend is also seen for the variants RR and YR. The effect is seen on both negatively and positively charged carbons, indicating that the difference between the variants is not caused by electrostatic interactions with the carbon surface. Electrostatic shielding experiments suggest that electrostatic repulsion between the adsorbed m-LA molecules, with a net charge of -2, may be responsible for the low adsorption. The other variants tested have a lower net charge and therefor experience lower intermolecular repulsion in the adsorbed state.

Adsorption↗

Complementary use of radiological skeletal survey and bone scintigraphy in detection of bony injuries in suspected child abuse.

AIM: To compare the effectiveness of radiological skeletal survey and bone scintigraphy for the detection of bony injuries in cases of suspected child abuse. METHODS: All cases with a discharge diagnosis of child abuse that presented to the Royal Children's Hospital between 1989 and 1998 were retrieved, and those children that had undergone both skeletal survey and bone scintigraphy (radioisotope bone scan) within a 48 hour period were included in this study. Both examinations followed rigid departmental protocols and protocols remained identical throughout the timeframe of the study. The reports of the skeletal surveys and bone scans were retrospectively reviewed by a paediatric radiology fellow and consultant paediatric radiologist. RESULTS: The total number of bony injuries identified was 124 in 30 children. Of these, 64 were identified on bone scan and 77 on skeletal survey. Rib fractures represented 60/124 (48%) of the bony injuries and were present in 16/30 children (53%), of which 62.5% had multiple rib fractures. Excluding rib fractures, there were 64 (52%) bony injuries, of which 33% were seen on both imaging modalities, 44% were seen on skeletal survey only, and 25% were seen on bone scans alone. Metaphyseal lesions typical of child abuse were present in 20 cases (31%) on skeletal survey; only 35% of these were identified on bone scan. Six children (20%) had normal skeletal surveys, with abnormalities shown on bone scan. There were three children (10%) with normal bone scans who were shown to have injuries radiographically. CONCLUSIONS: Skeletal survey and bone scintigraphy are complementary studies in the evaluation of non-accidental injury, and should both be performed in cases of suspected child abuse.

Arm Injuries↗

The metabolic effects of short-term administration of physiological versus high doses of GH therapy in GH deficient adults.

OBJECTIVE: GH treatment has demonstrated favourable effects on most features of GH deficiency in hypopituitary adults. However, most studies employed supraphysiological GH doses, resulting in deterioration in insulin sensitivity (SI). The short-term metabolic effects of physiological doses of GH therapy in GH deficient (GHD) adults are largely unknown. We therefore compared the effects of short-term administration of two 'physiological' ('lowest' dose: 0.0017 mg/kg/day; 'low' dose: 0.0033 mg/kg/day) with two 'supraphy-siological' ('high' dose: 0.010 mg/kg/day; 'highest' dose: 0.025 mg/kg/day) GH doses on SI, beta-cell function, IGF-1 and IGFBPs -1 and -3 in a group of GHD adults. PATIENTS AND METHODS: Thirteen GHD adults were recruited (seven men, aged 23-63 years). For each of the four doses, six patients (three men) were allocated randomly to undergo a 7-day treatment phase. Fasting blood samples were collected daily (days 1-8), and SI and beta-cell function were calculated using the homeostasis model assessment (HOMA). RESULTS: All four GH doses increased IGF-1, IGFBP-3 and IGF-1/IGFBP-3 ratio, and decreased IGFBP-1 from day 3 onwards (P < 0.05). The highest dose increased fasting glucose (P < 0.001), insulin (P < 0.001) and beta-cell function (P < 0.001), but decreased SI (P < 0.001). The high and low doses did not modify fasting glucose and insulin, SI or beta-cell function, whereas the lowest dose enhanced beta-cell function (P < 0.05). The overall increase in the GH dose increased IGF-1, IGFBP-3, fasting glucose and insulin (P < 0.001), demonstrated a positive correlation with the final change in fasting glucose (r = 0.5, P < 0.05) and insulin (r = 0.8, P < 0.001) and a negative correlation with final SI (r = -0.5, P < 0.05). CONCLUSIONS: Our results suggest that short-term administration of the highest GH dose induced insulin resistance, whereas the lowest dose (0.0017 mg/kg/day) could represent the optimal starting dose in GHD adults due to its beneficial effects on beta-cell function without compromising SI. It is, however, yet to be determined whether the positive effects of the lowest GH dose on beta-cell function can be demonstrated over a longer period of time.

Adult↗

Vitamin K deficiency and D-dimer levels in the intensive care unit: a prospective cohort study.

Patients in the intensive care unit (ICU) are at risk for the development of vitamin K deficiency. We sought to determine the frequency of this deficiency by performing a prospective cohort study in which patients were screened for vitamin K deficiency on ICU admission and every other day thereafter. Vitamin K deficiency was diagnosed by a functional coagulation factor II to Echis factor II ratio < 0.70. Activity of the coagulation cascade was measured by D-dimer. In total, 40 patients were enrolled into the study. Seven of the patients had ratios < 0.70 on the day of admission to the ICU, and three patients developed ratios < 0.70. Thus, 10 of 40 patients (25%; 95% confidence interval, 12-38%) had vitamin K deficiency. Two patients developed coagulopathy, as indicated by an International Normalized Ratio of more than 1.4. D-dimer levels were elevated in 86 of 111 samples. We conclude that vitamin K deficiency is common among critically ill patients, particularly on admission to the ICU. Our findings suggest that additional clinical research is warranted to determine whether vitamin K supplementation on admission to the ICU reduces the risk of ICU-acquired vitamin K deficiency and its attendant complications over the course of the ICU stay.

Aged↗

Seasonal serum concentrations of melatonin in cycling and noncycling mares.

To determine whether secretory patterns of melatonin change throughout the seasons in mares, blood samples were drawn byvenipuncture from nine mares at noon and midnight for five successive days at monthly intervals from August through July at the University of Missouri in Columbia, MO. In addition, during September, December, March, and June, blood samples were drawn from indwelling catheters at 2-h intervals for 48 or 72 h. Mares were predominantly Quarter Horses weighing approximately 450 kg and ranged from 3 to 12 yr of age. Mares were housed in outdoor paddocks with three-sided run-in sheds for shelter. During the noon and midnight bleeding period, mares were placed in a larger open-sided barn with outside runs. Mares remained outdoors with the barn being used as a shelter in the event of inclement weather. All lights in the shed were converted to red light. Often, moonlight provided enough illumination to collect blood samples. Mares were returned to their normal paddock after each sampling period. For analysis of data, a mare was considered to be cycling if serum concentrations of progesterone were greater than 1 ng/ mL. For a mare to be classified as exhibiting a nocturnal rise of melatonin, serum concentrations of melatonin had to be at least two times greater at midnight than at noon. By month, a relationship did not exist (chi2; P > 0.05) among mares that were exhibiting estrous cycles and exhibiting nocturnal rises of melatonin. Likewise, examination of serum profiles of melatonin taken at 2-h intervals for 48 h revealed considerable variation among mares throughout the seasons. A nocturnal rise in serum melatonin was observed only in June (P < 0.02). In March and December, serum melatonin was greater in cycling mares than noncycling mares, but the elevation was not associated with light-dark periods (P < 0.01). Two of the mares exhibited estrous cycles throughout the seasons but melatonin secretion in these two mares were similar to that observed in the seven mares that demonstrated seasonal anestrous. From these results, it does not appear that changes in serum concentrations of melatonin are used as a cue to regulate cyclic activity in the mare throughout the seasons.

Anestrus↗

Prevention and diagnosis of venous thromboembolism in critically ill patients: a Canadian survey.

BACKGROUND: Venous thromboembolism (VTE) confers considerable morbidity and mortality in hospitalized patients, although few studies have focused on the critically ill population. The objective of this study was to understand current approaches to the prevention and diagnosis of deep venous thrombosis (DVT) and pulmonary embolism (PE) among patients in the intensive care unit (ICU). DESIGN: Mailed self-administered survey of ICU Directors in Canadian university affiliated hospitals. RESULTS: Of 29 ICU Directors approached, 29 (100%) participated, representing 44 ICUs and 681 ICU beds across Canada. VTE prophylaxis is primarily determined by individual ICU clinicians (20/29, 69.0%) or with a hematology consultation for challenging patients (9/29, 31.0%). Decisions are usually made on a case-by-case basis (18/29, 62.1%) rather than by preprinted orders (5/29, 17.2%), institutional policies (6/29, 20.7%) or formal practice guidelines (2/29, 6.9%). Unfractionated heparin is the predominant VTE prophylactic strategy (29/29, 100.0%) whereas low molecular weight heparin is used less often, primarily for trauma and orthopedic patients. Use of pneumatic compression devices and thromboembolic stockings is variable. Systematic screening for DVT with lower limb ultrasound once or twice weekly was reported by some ICU Directors (7/29, 24.1%) for specific populations. Ultrasound is the most common diagnostic test for DVT; the reference standard of venography is rarely used. Spiral computed tomography chest scans and ventilation-perfusion scans are used more often than pulmonary angiograms for the diagnosis of PE. ICU Directors recommend further studies in the critically ill population to determine the test properties and risk:benefit ratio of VTE investigations, and the most cost-effective methods of prophylaxis in medical-surgical ICU patients. INTERPRETATION: Unfractionated subcutaneous heparin is the predominant VTE prophylaxis strategy for critically ill patients, although low molecular weight heparin is prescribed for trauma and orthopedic patients. DVT is most often diagnosed by lower limb ultrasound; however, several different tests are used to diagnose PE. Fundamental research in critically ill patients is needed to help make practice evidence-based.

Anticoagulants↗

Increasing incidence of HIV infections among young gay and bisexual men in Vancouver.

Since the beginning of the HIV epidemic in north America, the majority of HIV infections have occurred among men who engage in sexual relations with other men. As the HIV epidemic enters its third decade, gay and bisexual men continue to have among the highest rates of HIV infection. Previous studies have highlighted the decline in the incidence of HIV and risk behaviour among gay and bisexual men. However, several studies have suggested that young gay and bisexual men continue to engage in unprotected sexual behaviours and are at continued risk of HIV infection. Recent reports in the media and research literature have indicated an increase in the incidence of HIV among gay and bisexual individuals in many of the world's major cities. The purpose of this study was to determine trends in HIV incidence using data from a prospective cohort of young gay and bisexual men.

Adolescent↗

Doctors' perceptions of the effects of interventions tested in prospective, randomised, controlled, clinical trials: results of a survey of ICU physicians.

OBJECTIVES: To establish a list of therapeutic interventions considered by intensive care unit (ICU) physicians to have been tested by prospective, randomised, controlled clinical trials (RCTs) in critically ill patients, and to survey the perceptions of the same physicians on the therapeutic effect of these interventions as evaluated by RCT. DESIGN AND SETTING: Self-applied questionnaire in an International Symposium of Intensive Care and Emergency Medicine, Brussels, Belgium. PARTICIPANTS: All 3250 registrants at the symposium. MEASUREMENTS AND RESULTS: There were 527 questionnaires completed, and 446 were suitable for analysis. Respondents were asked to list the therapeutic interventions used in intensive care medicine which they believed have been shown by RCTs to improve survival. Using a 5-point Likert scale, respondents were then asked to rate their assessment of the effectiveness of each intervention they listed and, using a 3-point scale, to select their level of confidence in those assessments. A total of 512 interventions were identified by the respondents as having been tested by RCT. Analysing the 42 interventions quoted more than 12 times, 31 were believed by the respondents to have been shown to have a beneficial effect, and 11 to have a harmful effect. Many of the interventions noted have not in fact been subjected to RCT. CONCLUSIONS: Many interventions that have not been tested by RCT were believed to have been tested; conversely, some interventions actually tested by RCT were not mentioned. Few interventions used in the ICU have actually been shown by RCT to have a positive effect on outcome.

Adult↗