Biomedical subjects
Publications and source records attributed to David Johnson.
Solid and papillary epithelial (SPEN) is an uncommon pancreatic tumor often seen in young females. Although most of these neoplasms have a benign course, SPEN do have malignant potential. Treatment is surgical which is usually feasible either via enucleation or more radical procedures. Below we discuss diagnosis, treatment, and prognosis in detail.
PURPOSE: To describe the use of high frequency oscillatory ventilation (HFOV) in the management of a high output bronchopleural fistula (BPF). CLINICAL FEATURES: A 55-yr-old female developed a BPF after thoracotomy and decortication of an empyema. The patient deteriorated on the second postoperative day (pH 7.10 PCO2 89) requiring 100% oxygen and mechanical ventilation. After initial improvement, deterioration occurred by 24 hr with conventional positive pressure ventilation (volume or pressure limited) because of decreased pulmonary compliance and bilateral diffuse airspace disease (acute respiratory distress syndrome), persistent increased peak and plateau airway pressures, a prolonged inspired oxygen concentration greater than 0.6, and inability to apply positive end expiratory pressures because of an increased BPF leak (530 mL.breaths(-1)). HFOV was initiated and maintained for 28 days until resolution of the airspace disease and decreased leak through the BPF to 100 mL.breaths(-1). CONCLUSION: We report the successful use of HFOV in a patient with high output BPF. We suggest that HFOV is a useful technique in patients with a BPF when conventional positive pressure ventilation fails.
BACKGROUND: We assessed the incidence and prevalence of congestive heart failure (CHF) in patients diagnosed at the time of hospitalization and patients diagnosed in specialists offices without prior hospitalization in order to compare the trends in Canada with previously published trends in the USA and other industrialized countries. METHODS: Administrative data for Alberta, Canada from 1 April 1994 to 31 March 2000. RESULTS: There was a small but statistically significant decline in the age-sex incident and prevalent hospitalization rates for CHF between 1994/1995 (incidence per 1000 of 1.59; 99% CI 1.51, 1.66: prevalence per 1000 of 2.31; 99% CI 2.22, 2.40) and the year 1999/2000 (incidence per 1000 of 1.24; 99% CI 1.18, 1.30: prevalence per 1000 of 1.97; 99% CI 1.89, 2.05). Crude hospitalization rate per 1000 also demonstrated a small but statistically significant decline between 1994/1995 (2.98; 99% CI 2.88, 3.08) and 1999/2000 (2.55; 99% CI 2.46, 2.64). The age-sex incident rates of ambulatory diagnosis of CHF were similar throughout the 1994/1995-1999/2000 time period (0.88; 99% CI 0.82, 0.94 during 1994/1995 and 0.84; 99% CI 0.79, 0.89 during 1999/2000). The crude mortality percentage for incident hospitalization for CHF were similar throughout the 1994/1995-1999/2000 time period (31.0%; 99% CI 28.7, 33.3 during 1994/1995 and 28.6%; 99% CI 26.3, 30.9 during 1999/2000). CONCLUSIONS: We noted a small decrease in the incident, prevalent, and total hospitalizations for CHF in the time period 1994/1995-1999/2000. The decrease was not the result of a substituted increase in ambulatory diagnosis for CHF.
BACKGROUND: Cardiac mortality is the main cause of death in patients with chronic kidney disease (CKD). In this study, we sought the efficacy of long-term intensive lipid level lowering on atherosclerotic burden in patients with CKD. METHODS: Patients with CKD (n = 38; age, 64 +/- 11 years) and a similar group of patients with coronary artery disease (CAD; n = 31) were treated prospectively with atorvastatin, up to 80 mg/d. Lipid profile, carotid intima-media thickness (IMT; a marker of atherosclerotic burden), and dobutamine echocardiography were measured at baseline and 2 years. Predictors of change in maximal IMT were sought in a linear model. RESULTS: Despite similar cholesterol level lowering, patients with CAD showed an improvement in maximum IMT, whereas those with CKD did not (mean between-group difference, 0.07 mm; 95% confidence interval, 0.01 to 0.12). Change in maximal IMT was associated with kidney disease (R2 = 0.09; P = 0.013), smoking (R2 = 0.083; P = 0.017), baseline low-density lipoprotein cholesterol (LDL-C) level (R2 = 0.064; P = 0.045), very low density cholesterol (VLDL-C) level (R2 = 0.084; P = 0.021), and calcium channel blocker use (R2 = 0.094; P = 0.01). In a multivariate model, kidney disease and baseline LDL-C and VLDL-C levels remained independent predictors of change in maximal IMT (model R2 = 0.24; P = 0.004). Only patients with CAD decreased their number of ischemic segments (2.5 +/- 1.4 to 1.2 +/- 1.5 segments; P = 0.002). Overall change in ischemic segment number correlated with change in maximal IMT (r = 0.32; P = 0.019). CONCLUSION: Patients with CKD undergoing intensive lipid level lowering do not show the same changes in atherosclerotic or ischemic burden as patients with CAD. Independent predictors of change in maximal IMT were CKD and baseline LDL-C and VLDL-C levels.
An ensemble-trajectory analysis technique known as Quantitative Transport Bias Analysis was applied to determine which geographic areas systematically contributed to above- and below-average fine particle mass (PM2.5) over eastern North America. Six-hour average measurements from 12 rural or suburban locations in eastern North America collected using a tapered element oscillating microbalance were individually associated with corresponding 3-day back-trajectories for the warm seasons (May-September) of 2000 and 2001. Much of the populated areas of northeastern North America were implicated in the build-up of PM2.5 to above-average concentrations. The finer structure of the Quantitative Transport Bias Analysis pattern indicated that transport from the Ohio River Valley, particularly the eastern portion of this area, was most often associated with the highest PM2.5 concentrations. In addition, air masses originating over a relatively large area from southeast Ohio to the western part of Virginia and the western Kentucky to central Tennessee area tended to result in relatively high PM2.5 concentrations over northeastern North America. These observation-based findings were consistent with the spatial distribution of the main sulfur dioxide emissions sources and the major oxides of nitrogen point sources.
As many as 15 to 50% of end-stage kidney disease patients are on peritoneal dialysis (PD), but peritonitis limits its more widespread use. Several PD catheter-related interventions (catheter designs, surgical insertion approaches, and connection methods) have been purported to reduce the risk of peritonitis in PD. The goal was to assess the trial evidence supporting their use. The Cochrane CENTRAL Registry, MEDLINE, EMBASE, and reference lists were searched for randomized trials of catheter types and related interventions in PD. Two reviewers extracted data on the rates of peritonitis and exit-site/tunnel infection, catheter removal/replacement, technique failure, and all-cause mortality. Analysis was by a random effects model, and results are expressed as relative risk and 95% confidence intervals. Thirty-seven eligible trials (2822 patients) were identified: eight of surgical strategies of catheter insertion, eight of straight versus coiled catheters, 10 of Y-set versus conventional spike systems, four of Y-set versus double-bag systems, and seven of other interventions. Despite the large total number of patients, few trials covered the same interventions, small numbers of patients were enrolled in each trial, and the methodologic quality was suboptimal. Y-set and twin-bag systems were superior to conventional spike systems (seven trials, 485 patients; relative risk, 0.64; 95% confidence intervals 0.53 to 0.77), and no other catheter-related intervention was demonstrated to prevent peritonitis in PD. This systematic review demonstrates that of all catheter-related interventions designed to prevent peritonitis in PD, only disconnect (twin-bag and Y-set) systems have been proved to be effective (compared with conventional spike systems). Despite the importance of PD as a renal replacement therapy modality and the large number of patients who receive it, it is still not known whether any particular PD catheter designs, implantation techniques, or modalities are effective, given the limitations of available trials.
OBJECTIVES: The objectives of our study were to accurately describe the costs and resources required to treat survivors of severe sepsis subsequent to hospital discharge and to determine what factors influenced these costs. DESIGN: Observational cohort study. SETTING: Three regional intensive care units. PATIENTS: Patients with severe sepsis admitted to one of three regional intensive care units in southern Alberta between April 1, 1996, and March 31, 1999. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were identified using an intensive care unit research database; all survivors were followed prospectively for 3 yrs. Information on baseline patient characteristics, including acuity of illness (Acute Physiology and Chronic Health Evaluation II scores) and Charlson comorbidity scores, was collected. Costs considered included all episodes of inpatient and outpatient care and all physician claims. Of 787 patients who were admitted with severe sepsis, 502 survived to hospital discharge and were followed. Subsequent mean cost of care for years 1, 2, and 3 was CAN$20,855, $7,139 and $7,091, respectively. Using various regression models, the Acute Physiology and Chronic Health Evaluation II score and the Charlson comorbidity score were the only factors that consistently predicted higher healthcare costs in the first year after hospital discharge. Diabetes was the comorbid condition that best predicted subsequent cost. CONCLUSIONS: Cost of care for survivors of severe sepsis was highest in the first year after hospital discharge. Acuity of illness and patient comorbidity were the main determinants of cost. In assessing whether new therapeutic innovations for intensive care unit patients with severe sepsis are cost-effective, an accurate estimate of the cost of subsequent health care for survivors treated with and without the new intervention will be important.
Proteome-scale studies of protein three-dimensional structures should provide valuable information for both investigating basic biology and developing therapeutics. Critical for these endeavors is the expression of recombinant proteins. We selected Caenorhabditis elegans as our model organism in a structural proteomics initiative because of the high quality of its genome sequence and the availability of its ORFeome, protein-encoding open reading frames (ORFs), in a flexible recombinational cloning format. We developed a robotic pipeline for recombinant protein expression, applying the Gateway cloning/expression technology and utilizing a stepwise automation strategy on an integrated robotic platform. Using the pipeline, we have carried out heterologous protein expression experiments on 10,167 ORFs of C. elegans. With one expression vector and one Escherichia coli strain, protein expression was observed for 4854 ORFs, and 1536 were soluble. Bioinformatics analysis of the data indicates that protein hydrophobicity is a key determining factor for an ORF to yield a soluble expression product. This protein expression effort has investigated the largest number of genes in any organism to date. The pipeline described here is applicable to high-throughput expression of recombinant proteins for other species, both prokaryotic and eukaryotic, provided that ORFeome resources become available.
We hypothesized that myocardial infarction-related alterations in ventricular fibrillation (VF) cycle length (VFCL) would correlate with changes in local cardiac electrophysiological and anatomic properties. An electrophysiological study was performed in normal, subacute, and chronic infarction mongrel dogs. VF was induced by programmed electrical stimulation and mean and minimum early and late VFCL was determined and correlated with local electrophysiological and anatomic properties. Effective refractory period (ERP), activation recovery time (ART), ERP/ART ratio, threshold, and ERP and ART dispersion were determined at 112 sites on the anterior left ventricle. Wave front progression was analyzed over a 2-s period. The extent of local tissue necrosis and of myocardial fiber disarray was also evaluated. The early mean VFCL was significantly longer in the subacute infarction (149 +/- 35 ms) and chronic infarction dogs (129 +/- 18 ms) compared with control dogs (102 +/- 15 ms; P < 0.0001 for both comparisons) as was the early minimum VFCL with similar trends seen during late VF. Complete epicardial reentrant circuits were significantly more common in normal dogs (4.3 +/- 2.4, 22.4% of cycles) than in subacute (0.75 +/- 0.96, 5.3% of cycles, P < 0.05 vs. normal) and chronic infarction dogs (1.3 +/- 1.3, 7.5% of cycles, P < 0.05 vs. normal). There was a poor correlation between the mean and minimum early and late VFCL and local electrophysiological and anatomic properties (R(2) < 0.2 for all comparisons) with a much better correlation between average mean and minimum VFCL (over the entire plaque) and global ERP and ART dispersion during early and late VF. In conclusion, VFCL in normal and infarcted myocardium shows a poor correlation with local ventricular electrophysiological and anatomic properties measured in sinus rhythm. However, there was a much better correlation between the average VFCL with global dispersion of repolarization. The lack of correlation between local VFCL and refractoriness and the infrequent occurrence of epicardial reentry suggests that intramural reentry may be the primary mechanism of VF in this model.
Most medical schools do not have a separate course in geriatrics, but rather incorporate geriatrics into existing courses. Tracking and assessing curriculum content is more difficult in this setting. This paper describes and compares two approaches to assess curriculum content in geriatrics: a survey of course directors and a course objectives review. The results suggest that course directors report more geriatric content when asked as part of a regular survey than they identify as specific course objectives. Course objectives may be more reflective of the actual emphasis placed on aging-related material in courses. These two approaches appear to be complementary. Medical educators may find both self-report and course objective analysis to be useful and complementary in tracking geriatric material in the undergraduate medical curriculum.
UNLABELLED: Home care services are provided to about 10% of those admitted to hospital for acute myocardial infarction and about 20% of those discharged from hospital. The use of home care in patients with an acute myocardial infarction is growing in Alberta over the brief time span of this four year study. Those that received home care prior to a hospitalization for acute myocardial infarction were "old and frail" with a high mortality rate during and after hospitalization. The provision of home care after hospitalization selected those patients that stay in hospital longer and required more hospital care. BACKGROUND: The use of home care before and after hospitalization for acute myocardial infarction is described. METHODS: Hospital discharge abstracts were used to identify patients hospitalized in alberta, canada for acute myocardial infarction which were then linked to home care administrative data. RESULTS: There were 12,648 patients with acute myocardial infarction from April 1, 1995 until March 31, 1999. Home care within 60 days prior to hospitalization was provided for 8.7% of patients with acute myocardial infarctions (n = 1097) which significantly (p = 0.023) increased from 7.6% in the fiscal year 1995/6 to 9.5% in the fiscal year 1998/9. Home care within 60 days after hospitalization was provided to 16.4% of patients with acute myocardial infarctions (n = 2076) which significantly (p < 0.000) increased from 14.1% in the fiscal year 1995/6 to 18.1% in fiscal year 1998/9. Recipients of home care were significantly older, had more comorbidities, and greater severity of illness, but were less likely to undergo coronary artery revascularization during hospitalization. After multivariate adjustment, length of hospital stay, 60 day re-admissions, and mortality were higher in those receiving home care post hospitalization. Nearly half of those receiving home care prior to hospitalization died within one year. 80% of those receiving home care prior to admission also received home care services after hospitalization. CONCLUSION: Those patients who received home care prior to a hospitalization for acute myocardial infarction were "old and frail" with a high mortality rate during and after hospitalization. The provision of home care after hospitalization selected those patients that stay in hospital longer and required more hospital care.
Toll-like receptor (TLR) agonists are being developed for use as vaccine adjuvants and as stand-alone immunomodulators because of their ability to stimulate innate and adaptive immune responses. Among the most thoroughly studied TLR agonists are the lipid A molecules that target the TLR4 complex. One promising candidate, monophosphoryl lipid A, which is a derivative of lipid A from Salmonella minnesota, has proven to be safe and effective as a vaccine adjuvant in > 120,000 human doses. A new class of synthetic lipid A mimetics, the aminoalkyl glucosaminide 4-phosphates (AGPs), have been engineered specifically to target human TLR4 and are showing promise as vaccine adjuvants and as monotherapeutic agents capable of eliciting nonspecific protection against a wide range of infectious pathogens. In this review, the authors provide an update of the preclinical and clinical experiences with the TLR4 agonists, MPL (Corixa Corporation) adjuvant and the AGPs.
BACKGROUND: The current survival trends in patients with acute myocardial infarction (AMI) are not known. A population-based study using administrative data to examine the short and long term survival of patients after AMI in Alberta between 1994 and 1999 was conducted. METHODS: AMI patients were identified from hospital discharge data. Temporal changes in the adjusted (age, sex, AMI anatomical location and comorbidities) fatality rate were analyzed in 19,928 AMI patients. RESULTS: The age- and sex-adjusted incidence of hospitalization for AMI in Alberta significantly declined from 169.6 per 100,000 population in 1994 to 160.8 per 100,000 in 1999 (P=0.03). The risk-adjusted in-hospital case fatality rate from all causes was 11.4% (95% CI 10.6% to 12.3%) in 1994 versus 9.2% (8.4% to 10.1%) in 1999; the 30-day case fatality rate was 12.6% (11.7% to 13.6%) in 1994 versus 10.1% (9.1% to 11.0%) in 1999; and the one-year case fatality rate was 19.0% (17.8% to 20.1%) in 1994 versus 14.9% (13.8% to 16.0%) in 1999. The percentage of hospitalized AMI patients who underwent coronary angiography within one year after admission rose from 48.2% in 1994 to 52.4% in 1999; percutaneous transluminal coronary angioplasty increased from 25.5% to 35.0% and coronary artery bypass surgery increased from 9.7% to 12.6%. Prescriptions for pharmacological drugs at discharge increased from 1994 to 1999 among patients aged 65 and older: from 29.5% in 1994 to 41.0% in 1999 for beta-blockers, from 5.2% to 18.7% for lipid lowering agents and from 14.0% to 20.5% for angiotensin-converting enzyme inhibitors. INTERPRETATION: There was a modest improvement in patient survival after AMI between 1994 and 1999. The improvements may be associated with increasing use of revascularization and pharmacological therapy provided in the management of AMI.
BACKGROUND: The religious beliefs and spirituality of patients on hemodialysis (HD) therapy have not been studied extensively. Studies of the dialysis population seem to indicate that religion may be associated with increased patient satisfaction with life and increased levels of social support. METHODS: Using multiple religiosity scales and scales to assess patient satisfaction with life and social support, we studied the relationship between religiosity and medical and/or social factors and adherence to treatment in 74 HD patients. RESULTS: High scores on the Intrinsic Religiosity Scale were associated strongly with high scores on the Satisfaction With Life Scale, whereas age and high Organizational Religious Activity Scale scores were associated strongly with high scores on the Satisfaction With Medical Care Scale. Older age was associated strongly with increased adherence. No relationship existed between religiosity and adherence in our population. CONCLUSION: Religious beliefs are related strongly to measures of satisfaction with life, whereas religious behaviors are related to satisfaction with medical care. Age is the single most important demographic factor associated with adherence. Because of the complex nature of religiosity, additional investigation is in order.
BACKGROUND: A large proportion (15% to 50%) of the end-stage renal disease population are on peritoneal dialysis (PD). The major limitation is peritonitis, which leads to technique failure, hospitalization, and increased mortality. Oral, nasal, and topical antibiotic prophylaxis; exit-site disinfectants; and other antimicrobial interventions are used to prevent it. This study was conducted to assess what evidence supports these approaches. METHODS: The Cochrane CENTRAL Registry, MEDLINE, EMBASE, and reference lists were searched for randomized trials of antimicrobial agents in patients on PD. Two reviewers extracted data on the number of patients with 1 or more episodes and rates of peritonitis and exit-site and tunnel infection, catheter removal and/or replacement, technique failure, antibiotic toxicity, and all-cause mortality. Analysis was by means of a random-effects model, and results are expressed as relative risk (RR) and 95% confidence intervals (CI). RESULTS: Nineteen eligible trials (1,949 patients) were identified. Nasal mupirocin compared with placebo significantly reduced the exit-site and tunnel infection rate (1 trial; 2,716 patient-months; RR, 0.58; 95% CI, 0.40 to 0.85), but not peritonitis rate (1 trial; 2,716 patient-months; RR, 0.84; 95% CI, 0.44 to 1.60). Perioperative intravenous antibiotic therapy compared with no treatment significantly reduced the risk for early peritonitis (4 trials; 335 patients; RR, 0.35; 95% CI, 0.15 to 0.80), but not exit-site and tunnel infection (3 trials; 114 patients; RR, 0.32; 95% CI, 0.02 to 4.81). CONCLUSION: Based on 1 study, nasal mupirocin reduces exit-site and tunnel infection, but not peritonitis. Based on 4 studies, preoperative intravenous prophylaxis reduces early peritonitis, but not exit-site and tunnel infection. No other antimicrobial intervention has proven efficacy. Given the large number of patients on PD therapy and the importance of peritonitis, the lack of adequately powered randomized trials to inform decision making about strategies to prevent peritonitis is striking.
We describe the age-specific outcomes for patients hospitalized with newly diagnosed congestive heart failure using administrative hospital abstracts from Alberta, Canada, from April 1, 1994, to March 31, 2000. Seniors (aged 65 years and older) constituted about 85 per cent of the 16,162 patients. Both co-morbidity and severity of illness tended to increase with age. The use of special care unit admissions, coronary artery diagnostic services (cardiac catheterization), and revascularization procedures (percutaneous transluminal coronary angioplasty/stenting, coronary artery bypass surgery) peaked in the 50-to 64-year age group and decreased with increasing age. Specialist/sub-specialist care, prescriptions of beta blockers and angiotensin-converting enzyme inhibitors / angiotensin receptor blockers decreased with age in seniors. Adjusted in-hospital, 1-year mortality and crude, age-specific 5-year mortality were significantly greater in those 75 years and older. Outcomes and process of care in patients with newly diagnosed congestive heart failure were not uniformly distributed with age. The elderly had greater mortality but received less therapy.
As part of the Monoclonal Anti-TNF: A Randomized Controlled Sepsis (MONARCS) trial, which enrolled patients with suspected sepsis, we sought to determine whether adequate antibiotic therapy was associated with a decreased mortality rate. The study enrolled 2634 patients, 91% of whom received adequate antibiotic therapy. The mortality rate among patients given adequate antibiotic treatment was 33%, versus 43% among patients given inadequate treatment (P<.001). We conclude that adequate antibiotic therapy results in a significant decrease in the crude mortality rate among patients suspected of sepsis.