Modulation of oxyhemoglobin-induced protein kinase C activation by tamoxifen.
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Animals↗
Biomedical subjects
D Cook
Publications and source records attributed to D Cook.
Genetic analysis of calcium spiking responses in nodulation mutants of Medicago truncatula.
The symbiotic interaction between Medicago truncatula and Sinorhizobium meliloti results in the formation of nitrogen-fixing nodules on the roots of the host plant. The early stages of nodule formation are induced by bacteria via lipochitooligosaccharide signals known as Nod factors (NFs). These NFs are structurally specific for bacterium-host pairs and are sufficient to cause a range of early responses involved in the host developmental program. Early events in the signal transduction of NFs are not well defined. We have previously reported that Medicago sativa root hairs exposed to NF display sharp oscillations of cytoplasmic calcium ion concentration (calcium spiking). To assess the possible role of calcium spiking in the nodulation response, we analyzed M. truncatula mutants in five complementation groups. Each of the plant mutants is completely Nod- and is blocked at early stages of the symbiosis. We defined two genes, DMI1 and DMI2, required in common for early steps of infection and nodulation and for calcium spiking. Another mutant, altered in the DMI3 gene, has a similar mutant phenotype to dmi1 and dmi2 mutants but displays normal calcium spiking. The calcium behavior thus implies that the DMI3 gene acts either downstream of calcium spiking or downstream of a common branch point for the calcium response and the later nodulation responses. Two additional mutants, altered in the NSP and HCL genes, which show root hair branching in response to NF, are normal for calcium spiking. This system provides an opportunity to use genetics to study ligand-stimulated calcium spiking as a signal transduction event.
Calcium↗
Noninvasive positive-pressure ventilation: a utilization review of use in a teaching hospital.
BACKGROUND: The use of noninvasive positive-pressure ventilation (NIPPV) for acute respiratory failure (ARF) has become more widespread over the past decade, but its prescription, use and outcomes in the clinical setting remain uncertain. The objective of this study was to review the use of NIPPV for ARF with respect to clinical indications, physician ordering, monitoring strategies and patient outcomes. METHODS: A total of 91 consecutive adult patients admitted between June 1997 and September 1998 to a university-affiliated tertiary care hospital in Hamilton, Ont., who received 95 trials of NIPPV for ARF were included in an observational cohort study. Data abstraction forms were completed in duplicate, then relevant clinical, physiologic, prescribing, monitoring and outcome data were abstracted from the NIPPV registry and hospital records. RESULTS: The most common indications for NIPPV were pulmonary edema (42 of 95 trials [44.2%]) and exacerbation of chronic obstructive pulmonary disease (23 of 95 trials [24.2%]). NIPPV was started primarily in the emergency department (62.1% of trials), however, in terms of total hours of NIPPV the most frequent sites of administration were the intensive care unit (30.9% of total hours) and the clinical teaching unit (20.2% of total hours). NIPPV was stopped in 48.4% of patients because of improvement and in 25.6% because of deterioration necessitating endotracheal intubation. The median time to intubation was 3.0 hours (interquartile range 0.8-12.2 hours). The respirology service was consulted for 28.4% of the patients. Physician orders usually lacked details of NIPPV settings and monitoring methods. We found no significant predictors of the need for endotracheal intubation. The overall death rate was 28.6%. The only independent predictor of death was a decreased level of consciousness (odds ratio 2.9, 95% confidence interval 1.0-8.4). INTERPRETATION: NIPPV was used for ARF of diverse causes in many hospital settings and was started and managed by physicians with various levels of training and experience. The use of this technique outside the critical care setting may be optimized by a multidisciplinary educational practice guideline.
Adult↗
Syntheses of nucleoside triphosphates.
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Journal Article↗
Effect of smoking cessation on mortality after myocardial infarction: meta-analysis of cohort studies.
OBJECTIVE: To determine the effect of smoking cessation on mortality after myocardial infarction. DATA SOURCES: English- and non-English-language articles published from 1966 through 1996 retrieved using keyword searches of MEDLINE and EMBASE supplemented by letters to authors and searching bibliographies of reviews. STUDY SELECTION: Selection of relevant abstracts and articles was performed by 2 independent reviewers. Articles were chosen that reported the results of cohort studies examining mortality in patients who quit vs continued smoking after myocardial infarction. DATA EXTRACTION: Mortality data were extracted from the selected articles by 2 independent reviewers. DATA SYNTHESIS: Twelve studies were included containing data on 5878 patients. The studies took place in 6 countries between 1949 and 1988. Duration of follow-up ranged from 2 to 10 years. All studies showed a mortality benefit associated with smoking cessation. The combined odds ratio based on a random effects model for death after myocardial infarction in those who quit smoking was 0.54 (95% confidence interval, 0.46-0.62). Relative risk reductions across studies ranged from 15% to 61%. The number needed to quit smoking to save 1 life is 13 assuming a mortality rate of 20% in continuing smokers. The mortality benefit was consistent regardless of sex, duration of follow-up, study site, and time period. CONCLUSION: Results of several cohort studies suggest that smoking cessation after myocardial infarction is associated with a significant decrease in mortality.
Age Factors↗
Gay and lesbian physicians in training: a qualitative study.
BACKGROUND: Gay and lesbian physicians in training face considerable challenges as they become professionalized. Qualitative research is necessary to understand the social and cultural factors that influence their medical training. In this study we explored the significance of gay or lesbian identity on the experiences of medical training using naturalistic methods of inquiry. METHODS: Semi-structured interviews, focus groups and an e-mail listserv were used to explore professional and personal issues of importance to 29 gay and lesbian medical students and residents in 4 Canadian cities. Data, time, method and investigator triangulation were used to identify and corroborate emerging themes. The domains explored included career choice, "coming out," becoming a doctor, the environment and career implications. RESULTS: Gay or lesbian medical students and residents experienced significant challenges. For all participants, sexual orientation had an effect on their decisions to enter and remain in medicine. Once in training, the safety of a variety of learning environments was of paramount importance, and it affected subsequent decisions about identity disclosure, residency and career path. Respondents' assessment of professional and personal risk was influenced by the presence of identifiable supports, curricula inclusive of gay and lesbian sexuality and health issues and effective policies censuring discrimination based on sexual orientation. The need for training programs to be proactive in acknowledging and supporting diversity was identified. INTERPRETATION: Considerable energy and emotion are spent by gay and lesbian medical students and residents navigating training programs, which may be, at best, indifferent and, at worst, hostile.
Adult↗
Development, dissemination, implementation and evaluation of a clinical pathway for oxygen therapy.
BACKGROUND: Oxygen is commonly administered to patients in hospital, but prescribing and monitoring of such therapy may be suboptimal. The objective of this study was to develop, disseminate, implement and evaluate a multidisciplinary clinical pathway for the administration of oxygen. METHODS: The authors developed a clinical pathway for the ordering, titration and discontinuation of oxygen, which was disseminated through teaching sessions, in-service training sessions and information posters in a medical clinical teaching unit (CTU). Implementation of the pathway was ensured by means of reminders and patient-centred audit and feedback to CTU nurses and house staff. During a 3-month intervention phase, consecutive patients requiring supplemental oxygen were treated according to the pathway. During a 1-month "wash-out" phase followed by a 3-month non-intervention phase, patients were treated at the discretion of the CTU team. Clinical and economic data were collected in both phases. RESULTS: In the 2 phases, patient characteristics, the concentration and duration of oxygen prescribed, the frequency of oxygen saturation monitoring, the frequency of arterial blood gas testing and the clinical outcomes were similar. However, there were more discontinuation orders in the intervention phase (p < 0.001). In the intervention phase, costs were higher for monitoring of oxygen saturation ($44.95/patient v. $36.17/patient, p = 0.048) and for order transcription ($2.71/patient v. $1.28/patient, p < 0.001); total costs, including those for personnel, were also higher in the intervention phase ($76.93/patient v. $56.67/patient, p = 0.02). The cost of education about the oxygen pathway was $45.71/patient. When the education cost was included, the total cost of oxygen therapy during the intervention phase was $122.64/patient; this was significantly higher than the total cost of oxygen therapy during the non-intervention phase ($56.67/patient) (p < 0.001). INTERPRETATION: This multidisciplinary, multimethod oxygen pathway led to changes in oxygen-prescribing behaviour, consumed more resources than standard management and was not associated with changes in patient outcome. Appropriate management of oxygen prescribing and monitoring by physicians and nurses take time and costs money.
Aged↗
Ventilator associated pneumonia: perspectives on the burden of illness.
OBJECTIVE: The objective of this narrative review is to summarize selected current concepts and clinical evidence regarding the burden of illness of VAP, including its epidemiology, diagnosis, attributable mortality and risk factors. DATA SOURCES & SELECTION: Studies were identified through MEDLINE, EMBASE, bibliographies of primary and review articles and personal files. RESULTS: While cross sectional studies inform us about VAP prevalence, longitudinal studies inform us of the cumulative risk and conditional risk of developing VAP. Reported VAP rates are modulated by factors related to case mix, causative microorganisms, interventions that influence risk over time, and VAP definitions employed. Population-specific and organism-specific VAP rates are needed to avoid misleading benchmarking between different ICUs, and to minimize inappropriate between-study comparisons. Observational studies have shown that invasive sampling techniques versus non-invasive approaches to diagnose VAP facilitates more targeted antibiotic treatment; however, the influence of the diagnostic method on endpoints such as mortality is less clear. VAP is associated with approximately a 4 day increase in length of ICU stay and an attributable mortality of approximately 20-30%. Fixed VAP risk factors include underlying cardiorespiratory disease, neurologic injury and trauma. Modifiable VAP risk factors include supine body position, witnessed aspiration, paralytic agents and antibiotic exposure. If modifiable risk factors tested in randomized trials lower VAP rates, such as semirecumbency versus supine positioning, these represent effective VAP prevention strategies. CONCLUSIONS: Ventilator-associated pneumonia is a major morbid outcome among critically ill patients. Studies evaluating more effective prevention and treatment strategies are needed.
Critical Illness↗
Using and understanding sedation scoring systems: a systematic review.
OBJECTIVE: To systematically review instruments for measuring the level and effectiveness of sedation in adult and pediatric ICU patients. STUDY IDENTIFICATION: We searched MEDLINE, EMBASE, the Cochrane Library and reference lists of the relevant articles. We selected studies if the sedation instrument reported items related to consciousness and one or more additional items related to the effectiveness or side effects of sedation. DATA ABSTRACTION: We extracted data on the description of the instrument and on their measurement properties (internal consistency, reliability, validity and responsiveness). RESULTS: We identified 25 studies describing relevant sedation instruments. In addition to the level of consciousness, agitation and synchrony with the ventilator were the most frequently assessed aspects of sedation. Among the 25 instruments, one developed in pediatric ICU patients (the Comfort Scale), and 3 developed in adult ICU patients (the Ramsay scale, the Sedation-Agitation-Scale and the Motor Activity Assessment Scale), were tested for both reliability and validity. None of these instruments were tested for their ability to detect change in sedation status over time (responsiveness). CONCLUSION: Many instruments have been used to measure sedation effectiveness in ICU patients. However, few of them exhibit satisfactory clinimetric properties. To help clinicians assess sedation at the bedside, to aid readers critically appraise the growing number of sedation studies in the ICU literature, and to inform the design of future investigations, additional information about the measurement properties of sedation effectiveness instruments is needed.
Adult↗
Visualization of data.
Data visualization has developed in several directions: theoretical; methodological; and in new application areas. Advances include the development of a grammar of graphics, deeper understanding of human perception and implications for graphical layout, and better approaches to visualizing multi-dimensional data and large data sets. Gene expression is a notable new application area for visualization of large data sets.
Biotechnology↗
Towards a "good" death: end-of-life narratives constructed in an intensive care unit.
End-of-life decisions regarding the withdrawal and withholding of life supporting technology have become commonplace within intensive care units (ICUs). In this paper, we examine the dialogue between ICU team members and families regarding limitation of treatment as a therapeutic narrative--that is, as a story which frames therapeutic events as well as the critically ill patient's experience in a meaningful and psychologically comforting way for families and health care providers alike. The key themes of these end-of-life narratives are discussed, as well as the qualities that the stories share with other narratives of the same genre.
Attitude of Health Personnel↗
Significant post-transplant hypogammaglobulinemia in six heart transplant recipients: an emerging clinical phenomenon?
BACKGROUND: The recent development of powerful agents such as mycophenolate mofetil and tacrolimus has altered current regimens for the prevention and treatment of allograft rejection. Questions have been raised about these newer regimens in terms of susceptibility to opportunistic infections and effects on host defenses. Severe hypogammaglobulinemia has been infrequently described in solid organ transplant recipients, but has been recently noted in six heart transplant recipients at one center, of whom five were receiving a combination of tacrolimus, mycophenolate mofetil, and prednisone. METHODS: Case summaries of six recent heart transplant recipients with total immunoglobulin G (IgG) levels of less than 310 mg/dl, five of whom had cytomegalovirus (CMV) infection and three of whom had multiple infections including Nocardia, invasive Trichophyton, and Acinetobacter bacteremia. Previous literature was reviewed with the aid of a Medline search using the search terms hypogammaglobulinemia; kidney, liver, heart, lung, and organ transplantation; mycophenolate mofetil; tacrolimus; cyclosporine; azathioprine; and nocardiosis. RESULTS: We here report six cardiac transplant recipients seen over a period of one year who were found to have immunoglobulin G levels of 310 mg/dl or below (normal: 717-1400 mg/dl). The first five patients were diagnosed because of evaluation for infections; the sixth, who was asymptomatic with an IgG level of 175, was found during screening for hypogammaglobulinemia instituted as a result of these first five patients. All six patients had received steroid pulses for rejection; all received mycophenolate mofetil; and 5/6 had been switched from cyclosporine to tacrolimus because of steroid-resistant rejection. Transient neutropenia (absolute neutrophil count less than 1000) was observed in 2/6; 3/6 had received OKT3 therapy for refractory rejection. These six patients were treated with a combination of antimicrobials, immunoglobulin replacement, and decrease in immunosuppressive therapy. CONCLUSION: The finding of unexpected hypogammaglobulinemia and concomitant infectious complications in six heart transplant recipients highlights a possible complication in a subset of patients receiving newer immunosuppressive agents. A larger prospective study is underway to determine risk factors for development of post-transplant hypogammaglobulinemia and to assess pre-transplant immune status of these recipients. Monitoring of immunoglobulin levels in high-risk patients receiving intensified immunosuppressive therapy for rejection may help to prevent infectious complications.
Acinetobacter Infections↗
Use of focus groups to assess the educational needs of the primary care physician for the management of asthma.
OBJECTIVES: To determine the educational needs of primary care physicians, in the management of patients with asthma. DESIGN: Focus group discussions with physicians, pharmacists, respiratory therapists and patients. SETTING: Metropolitan Edmonton, Alberta, Canada. PARTICIPANTS: Out of an original mail request to 100 potential recruits, 52 people attended the focus group sessions. These included physicians, pharmacists, respiratory therapists, adult patients and paediatric patients accompanied by their parents. MAIN OUTCOME MEASURE: Consensus of the specific group being interviewed using facilitator-mediated responses, to identify problems in the care of asthma patients and appropriate educational methods to improve the situation. RESULTS: Both diagnostic and treatment concerns were identified by the primary care physicians and others in the study. Confusion with infection was the most common diagnostic problem. Major treatment problems involved confusion about aspects of management strategy and a lack of communication between physicians, patients and other members of the health care team. Poor patient compliance and patients changing doctors frequently were also of major concern. There were inconsistencies in the treatment of asthma between physicians. While most physicians felt that they were up-to-date in management, Asthma Control Guidelines were seldom followed. CONCLUSIONS: There is an urgent need for continuing medical education, not only in management but also in communication with patients and with other members of the health care team. The data permit the development of an ongoing educational programme which is practical and designed to deal with the issues identified in this survey.
Alberta↗
Venous thromboembolic disease: an observational study in medical-surgical intensive care unit patients.
PURPOSE: Acute and chronic illness, immobility, and procedural and pharmacologic interventions may predispose patients in the intensive care unit (ICU) to venous thromboembolic (VTE) disease. The purpose of this study was to observe potential risk factors and diagnostic tests for VTE, and prophylaxis against VTE in medical-surgical ICU patients. MATERIALS AND METHODS: In a prospective observational study, 93 consecutive patients admitted to a mixed medical-surgical ICU were followed. We recorded demographics, admitting diagnoses, APACHE II score, VTE risk factors, antithrombotic, anticoagulant and thrombolytic agents, diagnostic tests for deep venous thrombosis (DVT) and pulmonary embolus (PE), and clinical outcomes. RESULTS: Patients were 65.5 (15.5) years old with an APACHE II score of 21.1 (9.0); 44 (47.3%) were female. Admission diagnoses were medical (58, 67.4%) and surgical (35, 37.6%). The duration of ICU stay was 3 days (interquartile range: 1, 8.5 days) and the ICU mortality rate was 20.4% (19 of 93). We observed 8 VTE events among 5 of 93 patients (incidence 5.4% [0.8 to 10.0]); 2 patients had DVT and PE before admission, 1 had DVT as an admitting diagnosis, 1 had DVT on day 2 and PE on day 3, and 1 had PE on day 2. Over 804 ICU patient-days, 2 of 5 ultrasound examinations diagnosed DVT and 2 of 3 ventilation-perfusion lung scans diagnosed PE. Of 64 patients in whom heparin was not contraindicated and who were not anticoagulated, subcutaneous heparin prophylaxis was prescribed for 40 (62.5%) patients. ICU-acquired VTE risk factors were mechanical ventilation (odds ratio [OR] 1.56), immobility (OR 2.14), femoral venous catheter (OR 2.24), sedatives (OR 1.52), and paralytic drugs (OR 4.81), whereas VTE heparin prophylaxis (OR 0.08), aspirin (OR 0.42), and thromboembolic disease stockings (OR 0.63) were associated with a lower risk. Only warfarin (OR 0.07, P =.01) and intravenous heparin (OR 0.04, P<.01) were associated with a significantly decreased risk of VTE. CONCLUSIONS: Several ICU-acquired risk factors for VTE were documented in this medical-surgical ICU. VTE prophylaxis was underprescribed, and VTE diagnostic tests were infrequent. Further research is required to determine the incidence, predisposing factors, attributable morbidity, mortality, and costs of VTE in medical-surgical ICU patients, the optimal diagnostic test strategies, and the most cost-effective approaches of prophylaxis.
APACHE↗
Exploring the clinical pharmacist's role in improving home care for patients with diabetes.
Diabetes is a common condition among clients receiving home care services. Improved glycemic control can greatly thwart the long-term complications of diabetes. A study examining the role of a clinical pharmacist was performed in a home care agency in which 105 clients were interviewed and their respective charts reviewed with the following results: 37% were incorrectly classified as to type of diabetes, serum creatinine and HbA1c values were not commonly recorded, and clients tended to have complex drug regimens with a large number of potential drug-related problems. The clinical pharmacist's potential impact in this environment is great based on the data gathered from this study.
Adult↗
Examination of the oral mucosa and peripheral blood cells of patients with recurrent aphthous ulceration for human herpesvirus DNA.
OBJECTIVE: The purpose of this study was to exam the oral mucosa and peripheral blood cells of patients with recurrent aph-thous ulceration (RAU) for the presence of the following human herpesviruses: herpes simplex viruses 1 and 2, varicella zoster virus, Epstein-Barr virus, cytomegalovirus, human herpesvirus-6, and human herpesvirus-7. STUDY DESIGN: Fifty-eight subjects with RAU and 10 control subjects were recruited at an academic referral center and enrolled in this prospective, nonrandomized, case-controlled study. Each of the subjects with RAU was seen during an acute episode, and swab specimens from lesional (RAU-acute/lesion) and clinically normal (RAU-acute/normal) oral mucosa were obtained. Each of 2 subjects with RAU was evaluated during more than one acute episode. Three subjects with RAU were seen between active episodes, and swab specimens were taken from clinically normal (RAU-convalescent) oral mucosa. Swab specimens from clinically normal (control/normal) oral mucosa were obtained from the control subjects. Peripheral blood specimens were obtained from subjects with RAU and control subjects at the time the swab specimens were performed. Through use of polymerase chain reaction, all swab and peripheral blood specimens were examined for the presence of human herpesvirus DNA. Statistical significance was determined by means of chi(2) analysis. RESULTS: Herpes simplex virus and human herpesvirus-6 were found in a higher percentage of mucosal specimens from the control subjects (herpes simplex virus, 4/10; human herpesvirus-6, 5/9) than from the subjects with RAU (RAU-acute/lesion: 3/45 herpes simplex virus, 13/53 human herpesvirus-6; RAU-acute/normal: 7/48 herpes simplex virus, 9/53 human herpesvirus-6). No difference was demonstrated between RAU-acute/lesion, RAU-acute/normal, and RAU-convalescent mucosal specimens for any of the human herpesviruses. Different human herpesviruses were identified from individual subjects with RAU during subsequent episodes of disease. Epstein-Barr virus (6/35), human herpesvirus-6 (3/40), and human herpesvirus-7 (7/43) were detected in the peripheral blood mononuclear cells during acute RAU but not in RAU-convalescent or control peripheral blood mononuclear cells. CONCLUSIONS: The detection of human herpesvirus DNA from the oral mucosa and peripheral blood mononuclear cells of patients with RAU appears to represent normal viral shedding rather than a direct causal mechanism in this disorder.
Adult↗
Use of a screen log to audit patient recruitment into multiple randomized trials in the intensive care unit. Canadian Critical Care Trials Group.
OBJECTIVE: To develop and evaluate a screen log for monitoring enrollment in multiple randomized clinical trials conducted in a single center. SETTING: University-affiliated 20-bed tertiary care medical-surgical intensive care unit (ICU). PATIENTS: Consecutive ICU patients admitted between April 1995 and March 1997. METHODS: We developed a screen log for multicentered studies conducted in our ICU. Using a multiple-project, unicenter perspective, we evaluated the screen log as a tool for monitoring eligibility and enrollment of patients in four multicentered randomized trials focused on stress ulcer prophylaxis, blood transfusion thresholds, immunotherapy for sepsis and mechanical ventilation strategies. RESULTS: The screen log was used as an instrument to monitor trial execution. We recorded all aspects of study enrollment and created a taxonomy of reasons for nonenrollment into each trial. We calculated enrollment efficiency rates and used these data to develop strategies to maximize accrual. The screen log became a communication tool that fostered research-oriented continuous quality improvement initiatives for the management of concurrently conducted randomized trials in our ICU. CONCLUSIONS: Intensivists participating in several clinical trials may be interested in monitoring and maximizing enrollment when conducting multiple studies and understanding the influence of each trial on enrollment into the others. The unicenter, multiple-project screen log is one tool that may help to achieve these goals.
Canada↗