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David Johnstone

Publications and source records attributed to David Johnstone.

12 recordsLinked to original sources
PubMed2003

Prevention of Heart Failure in Patients in the Heart Outcomes Prevention Evaluation (HOPE) Study.

BACKGROUND: Previous trials in the prevention of heart failure have been restricted to patients with low ejection fraction or hypertension. We assessed an angiotensin-converting enzyme (ACE) inhibitor, ramipril, to prevent the development of heart failure in high-risk patients without known low ejection fraction or heart failure. METHODS AND RESULTS: We randomly assigned 9297 patients to receive double-blind ramipril (10 mg daily) or matching placebo for 4.5 years. Death attributable to heart failure, hospitalization for heart failure, initiation of open-label ACE inhibitor for heart failure, or development of typical signs or symptoms of heart failure developed in 951 patients and was associated with a 4.01-fold increase in the risk of death (P<0.0001). The rate of developing heart failure was significantly increased with coronary disease (risk ratio, 2.17), microalbuminuria (1.82), left ventricular hypertrophy (1.47), increasing age (by decade, 1.37), and diabetes (1.36). Ramipril reduced new-onset heart failure rate from 11.5% to 9.0% (relative risk, 0.77; 95% CI, 0.68 to 0.87; P<0.0001). Ramipril consistently reduced heart failure rate both in those with (relative risk, 0.87) and those without an interim myocardial infarction (relative risk, 0.78). Ramipril also reduced the heart failure rate more in patients with baseline systolic pressure above the median (139 mm Hg) (relative risk, 0.67) compared with those below the median (relative risk, 0.91; P=0.024 for interaction of group by treatment). CONCLUSION: Ramipril significantly reduces the rate of development of heart failure in patients at high risk of cardiovascular events.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2003

Low pH, caprylate incubation as a second viral inactivation step in the manufacture of albumin. Parametric and validation studies.

Caprylate has long been used as a stabiliser for albumin solutions, as well as a precipitation agent for immunoglobulins, ceruloplasmin and more recently in removing contaminants during albumin purification. Its virucidal properties have been explored and it has been proposed that the non-ionised form of the caprylate acid disrupts the integrity of the lipid bilayer and membrane associated proteins of enveloped viruses. The studies reported here further explore the use of this fatty acid to inactivate lipid-enveloped viruses in albumin manufactured for therapeutic use. Caprylate concentrations considered above solubility limits were adopted. Acidic pH was used to maximise the percentage of non-ionised caprylate and elevated temperatures were used to enhance inactivation rates. Parameters were manipulated to determine the relationship between pH, temperature and caprylate: protein ratio. These studies demonstrated that elevated temperature and low pH were critical in achieving significant reduction in virus infectivity and that the rate and extent of inactivation was sensitive to changes in caprylate:protein ratio and to changes in pH. Final inactivation conditions of 10% w/v protein, 16 mM caprylate, pH 4.5 and 30 degrees C were chosen to minimise protein dimerisation and to achieve greater than 4 log(10)inactivation of the most resistant virus tested, bovine viral diarrhoea virus. Validation studies using both model and relevant blood borne viruses demonstrated this to be a robust and effective viral inactivation step and is complementary to the commonly used pasteurisation viral inactivation step, thus providing an additional margin of safety to this valuable therapeutic blood product.

Animals↗
PubMed2003

Improving cardiovascular outcomes in Nova Scotia (ICONS): a successful public-private partnership in primary healthcare.

Broadly defined, disease, or health management, is a focused application of resources to improve patient outcomes; its premise: things can be better. In particular, the gap between what best care could be, and what usual care is, can be reduced and, consequently, care and outcomes can be improved. This paper reviews the evolution of the partnership/measurement paradigm of disease management and considers its value in sustaining Canadian healthcare. Lessons from ICONS (Improving Cardiovascular Outcomes in Nova Scotia), a major public-private health partnership of physicians, nurses, pharmacists, patients and their advocacy groups, government and industry, are highlighted. Launched in 1997, ICONS' proof-of-concept phase ended in 2002. Due to its positive impact on the cardiovascular health of the population and its integrated and accountable administrative processes, ICONS became an operational program of the Nova Scotia Department of Health. This successful community-based partnership represents a major achievement in organizational behaviour in the arena of primary healthcare. It supports optimal care as evidence-based and seamless, recognizing the patient as the nucleus. It should be considered for other disease states and constituencies where the goals are closing care gaps and delivering the best health to the most people at the best cost.

Aged↗
PubMed2003

Who said that?

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Canada↗
PubMed2003

Phase I/II clinical study of pulsed paclitaxel radiosensitization for thoracic malignancy: a therapeutic approach on the basis of preclinical research of human cancer cell lines.

PURPOSE: A Phase I/II clinical study using pulsed low-dose paclitaxel and radiation for thoracic malignancy was conducted. The study was based on preclinical research of the effects of paclitaxel on apoptosis and the cell cycle in human cancer cell lines. EXPERIMENTAL DESIGN: Three human epithelial cancer cell lines were investigated for preclinical study. Cells were analyzed for apoptosis and cell cycle characteristics after paclitaxel treatment. The Phase I/II clinical trial for non-small cell lung cancer used pulsed low-dose paclitaxel three times/week with the starting dose of 15 mg/m(2). Daily thoracic radiotherapy was delivered in 1.8 Gy/fraction to 60-65 Gy for gross disease and to 45-58 Gy for microscopic disease. Timing of radiotherapy was delayed to allow for a minimum of 4 h for cell cycle progression. RESULTS: Forty-one patients have enrolled and 33 completed treatments. Seventeen patients completed the Phase I study, with an average primary tumor shrinkage of 83 +/- 8% (95% confidence interval). Tumor response rate was 100% for the Phase I study. Overall local control was 98%, and the survival rate was 46% at 1 year, 33% at 2 years, and 18% at 3 years. Toxicity was low with 3 of 18 patients having grade 3 pneumonitis and 3 of 18 patients having grade 3 esophagitis. There was no grade 4 pneumonitis, esophagitis, or hematological toxicity. CONCLUSIONS: Pulsed low-dose paclitaxel radiosensitization for non-small cell lung cancer resulted in a superior local control rate and comparable survival rate when compared with chemoradiation regimens using systemic dose chemotherapy. The regimen is associated with low toxicity and deserves additional investigation, particularly in patients with poor performance or older age, who cannot tolerate standard chemoradiation regimens.

Apoptosis↗
PubMed2003

Working together.

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Cardiology↗
PubMed2003

Recipes.

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Canada↗
PubMed2002

Ischemia Management with Accupril post bypass Graft via Inhibition of angiotensin coNverting enzyme (IMAGINE): a multicentre randomized trial - design and rationale.

BACKGROUND: Coronary artery bypass grafting (CABG) remains the revascularization treatment of choice for patients with severely symptomatic or life-threatening coronary artery disease (CAD). However, 9% to 25% of the patients undergoing CABG will suffer a recurrent ischemic event such as death, recurrent infarction, angina or repeat revascularization. The pathophysiological processes particular to the CABG procedure that may affect graft endothelial function are most active in the early phase after surgery. Angiotensin-converting enzyme (ACE) inhibition has been shown to be effective in reducing or preventing ischemic events in patients with and without left ventricular dysfunction, and in those at high risk for CAD. Nonetheless, no large clinical trail has investigated this role of ACE inhibition in preventing ischemic events early after CABG. OBJECTIVE: The Ischemia Management with Accupril post bypass Graft via Inhibition of angiotensin coNverting Enzyme (IMAGINE) study addressed whether ACE inhibition initiated early after CABG improves short and long term outcomes in patients after CABG. PATIENTS AND METHODS: This multicentre, multinational trial recruited 2204 patients with an uncomplicated course early after CABG from 55 to 65 medical care facilities in Canada, The Netherlands, Belgium and France. Eligible patients with normal left ventricular function were randomly assigned to placebo or quinapril (titrated up to 40 mg daily where possible) within seven to 10 days after CABG. All patients were followed up closely for a minimum of 12 months after random placement. The median treatment period is expected to be approximately 27 months.

Angiotensin-Converting Enzyme Inhibitors↗