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Biomedical subjects

Janet Martin

Publications and source records attributed to Janet Martin.

10 recordsLinked to original sources

The use of amiodarone for in-hospital cardiac arrest at two tertiary care centres.

BACKGROUND: Although amiodarone significantly increases survival to hospital admission when used in resuscitation of out-of-hospital pulseless ventricular tachycardia and fibrillation, there are limited data on its utility for in-hospital arrests. OBJECTIVES: To determine whether the use of amiodarone, as recommended by the year 2000 American Heart Association Advanced Cardiac Life Support guidelines, improved survival following its introduction to the resuscitation algorithm at two tertiary care institutions. METHODS: Charts of 374 cardiac resuscitations were retrospectively studied at the two institutions. Basic survival outcomes and demographic data were recorded for cardiac arrests with ventricular tachyarrhythmias qualifying for administration of antiarrhythmic agents. RESULTS: Qualifying rhythms were present in 95 patients. Clinical uptake of amiodarone was limited. In the 36 patients who received amiodarone, survival of resuscitation was 67% versus 83% (P=0.07) in the 59 patients receiving only other antiarrhythmic agents (chiefly lidocaine [94%]), while survival to discharge was 36.1% and 55.9% (P=0.06) in these two groups, respectively. CONCLUSIONS: Following two years' experience with the introduction of intravenous amiodarone for resuscitation in the institutions, use was less than 50% and no clinically observable survival benefit could be documented. Possible explanations for the difference between this experience and that found in out-of-hospital resuscitation trials include differing patient populations and operator bias during resuscitation. These results should provoke other institutions to question whether amiodarone has improved survival of cardiac arrest under the conditions prevailing in their hospitals. A patient registry or prospective, randomized trial will be required to assess what parameters affect the success of intravenous amiodarone for resuscitation in-hospital.

Amiodarone↗

Systemic gene-directed enzyme prodrug therapy of hepatocellular carcinoma using a targeted adenovirus armed with carboxypeptidase G2.

Hepatocellular carcinoma is the fifth most common cancer worldwide, and there is no effective therapy for unresectable disease. We have developed a targeted systemic therapy for hepatocellular carcinoma. The gene for a foreign enzyme is selectively expressed in the tumor cells and a nontoxic prodrug is then given, which is activated to a potent cytotoxic drug by the tumor-localized enzyme. This approach is termed gene-directed enzyme prodrug therapy (GDEPT). Adenoviruses have been used to target cancer cells, have an intrinsic tropism for liver, and are efficient gene vectors. Oncolytic adenoviruses produce clinical benefits, particularly in combination with conventional anticancer agents and are well tolerated. We rationalized that such adenoviruses, if their expression were restricted to telomerase-positive cancer cells, would make excellent gene vectors for GDEPT therapy of hepatocellular carcinoma. Here we use an oncolytic adenovirus to deliver the prodrug-activating enzyme carboxypeptidase G2 (CPG2) to tumors in a single systemic administration. The adenovirus replicated and produced high levels of CPG2 in two different hepatocellular carcinoma xenografts (Hep3B and HepG2) but not other tissues. GDEPT enhanced the adenovirus-alone therapy to elicit tumor regressions in the hepatocellular carcinoma models. This is the first time that CPG2 has been targeted and expressed intracellularly to effect significant therapy, showing that the combined approach holds enormous potential as a tumor-selective therapy for the systemic treatment of hepatocellular carcinoma.

Adenoviridae↗

Sicily statement on evidence-based practice.

BACKGROUND: A variety of definitions of evidence-based practice (EBP) exist. However, definitions are in themselves insufficient to explain the underlying processes of EBP and to differentiate between an evidence-based process and evidence-based outcome. There is a need for a clear statement of what Evidence-Based Practice (EBP) means, a description of the skills required to practise in an evidence-based manner and a curriculum that outlines the minimum requirements for training health professionals in EBP. This consensus statement is based on current literature and incorporating the experience of delegates attending the 2003 Conference of Evidence-Based Health Care Teachers and Developers ("Signposting the future of EBHC"). DISCUSSION: Evidence-Based Practice has evolved in both scope and definition. Evidence-Based Practice (EBP) requires that decisions about health care are based on the best available, current, valid and relevant evidence. These decisions should be made by those receiving care, informed by the tacit and explicit knowledge of those providing care, within the context of available resources. Health care professionals must be able to gain, assess, apply and integrate new knowledge and have the ability to adapt to changing circumstances throughout their professional life. Curricula to deliver these aptitudes need to be grounded in the five-step model of EBP, and informed by ongoing research. Core assessment tools for each of the steps should continue to be developed, validated, and made freely available. SUMMARY: All health care professionals need to understand the principles of EBP, recognise EBP in action, implement evidence-based policies, and have a critical attitude to their own practice and to evidence. Without these skills, professionals and organisations will find it difficult to provide 'best practice'.

Adult↗

Barriers to exotic animal medicine.

The obstacles discussed in this article can be overcome as training and continuing education in this field become more readily available, making work with these fascinating species a part of the repertoire of the small animal clinician. The scientific literature concerning these species is growing rapidly, and medical standards are improving steadily.

Animals↗

The use of intraservice work per unit of time (IWPUT) and the building block method (BBM) for the calculation of surgical work.

OBJECTIVE: We will review the contribution to the Medicare Fee Schedule (MFS) by the techniques of intensity of work per unit of time (IWPUT), the building block methodology (BBM), and the work accomplished by the American College of Surgeons General Surgery Coding & Reimbursement Committee (GSCRC) in using IWPUT/BBM to detect undervalued surgical procedures and recommend payment increases. SUMMARY BACKGROUND DATA: The MFS has had a major impact on surgeons' income since its introduction in 1992 by the Centers for Medicare and Medicaid (CMS) and additionally has been adopted for use by many commercial insurers. A major component of MFS is physician work, measured as the relative value of work (RVW), which has 2 components: time and intensity. These components are incorporated by: RVW = time x intensity. METHODS: This work formula can be rearranged to give the IWPUT, which has become a powerful tool to calculate the amount of RVW performed by physicians. Most procedures are valued by the total RVW in the global surgical package, which includes pre-, intra-, and postoperative care for a time after surgery. Summing these perioperative components into RVW is called the building block methodology (BBM). RESULTS: Using these techniques, the GSCRC increased the values for 314 surgery procedures during a recent CMS 5-year review, resulting in an increase to general surgeons of roughly 76 million dollars annually. CONCLUSIONS: The use of IWPUT/BBM has been instrumental to correct payment for undervalued surgical procedures. They are powerful methods to measure RVW across specialties and to solve reimbursement, compensation, and practice management problems facing surgeons.

Centers for Medicare and Medicaid Services, U.S.↗

Off pump coronary artery bypass graft surgery versus conventional coronary artery bypass graft surgery: a systematic review of the literature.

The recent development of off-pump coronary artery bypass (OPCAB) graft surgical techniques has led to numerous observational and several randomized trials that have investigated outcomes compared with the current gold standard of conventional on-pump coronary bypass (CCAB) graft surgery. This systematic review assesses the current randomized trials that compare OPCAB and CCAB. Numerous end points were investigated, including mortality, stroke, myocardial infarction, atrial fibrillation, blood transfusions, wound infections, and renal failure. In addition to these important outcomes, resource utilization markers were also examined such as hospital length of stay, intensive care unit length of stay, and duration of intubation/ventilation. Finally, when level I evidence from randomized trials was unavailable, level II evidence was examined. This was done for subgroup analysis, where currently no randomized trials exist, looking at OPCAB in high-risk patients. Recommendations were made as to who should receive OPCAB and the potential benefits in this patient population.

Coronary Artery Bypass↗

A Canadian clinical practice algorithm for the management of patients with nonvariceal upper gastrointestinal bleeding.

AIM: To use current evidence-based recommendations to provide a user-friendly clinical algorithm for the management of upper gastrointestinal bleeding, adapted to the Canadian environment. METHODS: A multidisciplinary consensus group of 25 participants representing 11 national societies used a seven-step approach to develop recommendations according to accepted standards. Sources of data included narrative and systematic reviews as well as published and new meta-analyses. A small writing subgroup subsequently created the algorithm. RESULTS: Recommendations emphasize appropriate initial resuscitation of the patient and a multidisciplinary approach to clinical risk stratification that determines the need for early endoscopy. Early endoscopy allows safe and prompt discharge of selected patients classified as low risk. Endoscopic hemostasis is reserved for patients with high-risk endoscopic lesions. Although monotherapy with injection or thermal coagulation is effective, the combination is superior to either treatment alone. High-dose intravenous proton-pump inhibition is recommended in patients who have undergone successful endoscopic therapy. Routine second-look endoscopy is not recommended. Patients with upper gastrointestinal bleeding secondary to ulcer disease should be tested and treated for Helicobacter pylori infection. CONCLUSIONS: This algorithm should facilitate appropriate risk stratification, use of endoscopic therapy and the appropriate utilization of proton-pump inhibition to optimize the care of patients with upper gastrointestinal bleeding. The algorithm should be customized to the resources of individual medical centres. Its application should be studied with appropriate outcomes recorded and validation performed.

Algorithms↗

Comparing the quality of oral anticoagulant management by anticoagulation clinics and by family physicians: a randomized controlled trial.

BACKGROUND: There is growing evidence that better outcomes are achieved when anticoagulation is managed by anticoagulation clinics rather than by family physicians. We carried out a randomized controlled trial to evaluate these 2 models of anticoagulant care. METHODS: We randomly allocated patients who were expected to require warfarin sodium for 3 months either to anticoagulation clinics located in 3 Canadian tertiary hospitals or to their family physician practices. We evaluated the quality of oral anticoagulant management by comparing the proportion of time that the international normalized ratio (INR) of patients receiving warfarin sodium was within the target therapeutic range +/- 0.2 INR units (expanded therapeutic range) while they were managed in anticoagulation clinics as opposed to family physicians' care over 3 months. We measured the rates of thromboembolic and major hemorrhagic events and patient satisfaction in the 2 groups. RESULTS: Of the 221 patients enrolled, 112 were randomly assigned to anticoagulation clinics and 109 to family physicians. The INR values of patients who were managed by anticoagulation clinics were within the expanded therapeutic range 82% of the time versus 76% of the time for those managed by family physicians (p = 0.034). High-risk INR values (defined as being < 1.5 or > 5.0) were more commonly observed in patients managed by family physicians (40%) than in patients managed by anticoagulation clinics (30%, p = 0.005). More INR measurements were performed by family physicians than by anticoagulation clinics (13 v. 11, p = 0.001). Major bleeding events (2 [2%] v. 1 [1%]), thromboembolic events (1 [1%] v. 2 [2%]) and deaths (5 [4%] v. 6 [6%]) occurred at a similar frequency in the anticoagulation clinic and family physician groups respectively. Of the 170 (77%) patients who completed the patient satisfaction questionnaire, more were satisfied when their anticoagulant management was managed through anticoagulation clinics than by their family physicians (p = 0.001). INTERPRETATION: Anticoagulation clinics provided better oral anticoagulant management than family physicians, but the differences were relatively modest.

Ambulatory Care Facilities↗

Three new prodrugs for suicide gene therapy using carboxypeptidase G2 elicit bystander efficacy in two xenograft models.

Three new prodrugs, [prodrug 1: 4-[bis(2-iodoethyl)amino]-phenyloxycarbonyl-L-glutamic acid; prodrug 2: 3-fluoro-4-[bis(2-chlorethyl)amino]benzoyl-L-glutamic acid; and prodrug 3: 3,5-difluoro-4-[bis(2-iodoethyl)amino]benzoyl-L-glutamic acid] have been assessed for use with a mutant of carboxypeptidase G2 (CPG2, glutamate carboxypeptidase, EC 3.4.17.11,) engineered to be tethered to the outer tumor cell surface (stCPG2(Q)3) as the activating enzyme in suicide gene therapy systems. All three of the prodrugs produce much greater cytotoxicity differentials between stCPG2(Q)3- and control beta-galactosidase (beta-gal)-expressing breast carcinoma MDA MB 361 and colon carcinoma WiDr cells (70- to 450-fold) than was previously observed (19- to 27-fold) with 4-[(2-chloroethyl)(2-mesyloxyethyl)amino]benzoyl-L-glutamic acid (CMDA). Prodrug 1 is the most effective antitumor agent in xenografts in mice inoculated with 100% stCPG2(Q)3-expressing MDA MB 361 cells, whereas prodrugs 2 and 3 are most effective when the percentage of stCPG2(Q)3-expressing cells is 50% or 10%. In nude mice bearing xenografts arising from inocula of 100% stCPG2(Q)3-expressing WiDr cells, prodrug 2 is the most effective antitumor agent. All three of the prodrugs produced histological evidence of substantial bystander cell killing in WiDr xenografts in which only 10% or 50% of the cells inoculated were expressing stCPG2(Q)3. We conclude that all three of the prodrugs are more effective therapeutically with stCPG2(Q)3 than is the previously described prodrug CMDA and, also, that the optimal choice of prodrug varies among different tumor types and that prodrugs, optimized for their bystander effect, are effective when only low percentages of cells in a tumor express CPG2.

Animals↗