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Biomedical subjects

G A Wells

Publications and source records attributed to G A Wells.

At least 37 records · Page 2Linked to original sources
PubMed2001

Cardiac troponin T predicts long-term outcomes in hemodialysis patients.

BACKGROUND: Increased plasma troponin T (cTnT), but not troponin I (cTnI), is frequently observed in end-stage renal failure patients. Although generally considered spurious, we previously reported an associated increased mortality at 12 months. METHODS: We studied long-term outcomes in 244 patients on chronic hemodialysis for up to 34 months, correlating the outcomes to plasma cTnT in routine predialysis samples. In addition, subsequent plasma samples at least 1 year later and within 6 months of data analysis were available in 97 patients and were used to identify patients with increasing plasma cTnT. The endpoints used were death and new or worsening coronary, cerebro-, and peripheral vascular disease and neuropathy. RESULTS: Transplantation occurred more frequently in patients with low initial cTnT: 31%, 13%, and 3% in the groups with cTnT < 0.010, 0.010-0.099, and > or = 0.100 microg/L, respectively. In the same groups, total deaths occurred in 6%, 43%, and 59% and cardiac deaths in 0%, 14%, and 24% of patients. In patients with follow-up samples, the group with increasing cTnT had a significantly increased death (relative risk, 2.0; P = 0.028). The increase was mainly in cardiac and sudden deaths. CONCLUSIONS: Higher plasma cTnT predicts long-term all-cause mortality in hemodialysis patients, even at concentrations < 0.100 microg/L, as does an increasing cTnT concentration over time.

Aged↗
PubMed2001

Physicians' accuracy and interrator reliability for the diagnosis of unstable meniscal tears in patients having osteoarthritis of the knee.

OBJECTIVE: To determine clinicians' accuracy and reliability for the clinical diagnosis of unstable meniscus tears in patients with symptomatic osteoarthritis of the knee. DESIGN: A prospective cohort study. SETTING: A single tertiary care centre. PATIENTS: One hundred and fifty-two patients with symptomatic osteoarthritis of the knee refractory to conservative medical treatment were selected for prospective evaluation of arthroscopic debridement. INTERVENTION: Arthroscopic debridement of the knee, including meniscal tear and chondral flap resection, without abrasion arthroplasty. OUTCOME MEASURES: A standardized assessment protocol was administered to each patient by 2 independent observers. Arthroscopic determination of unstable meniscal tears was recorded by 1 observer who reviewed a video recording and was blinded to preoperative data. Those variables that had the highest interobserver agreement and the strongest association with meniscal tear by univariate methods were entered into logistic regression to model the best prediction of resectable tears. RESULTS: There were 92 meniscal tears (77 medial, 15 lateral). Interobserver agreement between clinical fellows and treating surgeons was poor to fair (kappa < 0.4) for all clinical variables except radiographic measures, which were good. Fellows and surgeons predicted unstable meniscal tear preoperatively with equivalent accuracy of 60%. Logistic regression modelling revealed that a history of swelling and a ballottable effusion were negative predictors. A positive McMurray test was the only positive predictor of unstable meniscal tear. "Mechanical" symptoms were not reliable predictors in this prospective study. The model was 69% accurate for all patients and 76% for those with advanced medial compartment osteoarthritis defined by a joint space height of 2 mm or less. CONCLUSIONS: This study underscored the difficulty in using clinical variables to predict unstable medial meniscal tears in patients with pre-existing osteoarthritis of the knee. The lack of interobserver agreement must be overcome to ensure that the findings can be generalized to other physician observers.

Adult↗
PubMed2001

The effect of low dose methotrexate on bone density.

OBJECTIVE: High dose methotrexate (MTX) has been linked with bone loss in oncology patients. However, it is unclear whether longterm low dose MTX used in the treatment of inflammatory arthritis is associated with bone loss. We compared the effect of low dose MTX on bone density in prospectively recruited patients with rheumatoid arthritis (RA) and psoriasis/psoriatic arthritis (Ps/PsA). METHODS: Thirty RA patients and 30 Ps/PsA patients taking MTX were compared to controls not taking MTX (30 with RA, 27 Ps/PsA). Bone mineral density (BMD) of the radius, lumbar spine, trochanter, and femoral neck was measured using Lunar dual energy x-ray absorptiometry. Student t tests were used to detect differences in bone density (using Z scores) of the MTX group versus controls for both the RA and Ps/PsA groups. Analysis of covariance was used to examine for confounders including disease duration, disease activity, age, and sex. RESULTS: BMD of the radius/femoral neck/trochanter did not differ significantly between the MTX treated groups and controls when analyzed by Z scores. The mean difference between the MTX group and controls of the femoral neck was 0.040 (95% CI -0.40, 0.12) and 0.060 (95% CI -0.30, 0.15) for the RA and Ps/PsA groups, respectively. The absolute BMD of the lumbar spine (L2-L4) was higher in the RA MTX group than in controls. Analysis of covariance did not reveal an effect of study group on bone density. CONCLUSION: This study suggests that low dose MTX does not have a negative effect on bone density, at either cortical or trabecular sites.

Absorptiometry, Photon↗
PubMed2000

Neonatal and fetal methylenetetrahydrofolate reductase genetic polymorphisms: an examination of C677T and A1298C mutations.

Methylenetetrahydrofolate reductase (MTHFR) mutations are commonly associated with hyperhomocysteinemia, and, through their defects in homocysteine metabolism, they have been implicated as risk factors for neural tube defects and unexplained, recurrent embryo losses in early pregnancy. Folate sufficiency is thought to play an integral role in the phenotypic expression of MTHFR mutations. Samples of neonatal cord blood (n=119) and fetal tissue (n=161) were analyzed for MTHFR C677T and A1298C mutations to determine whether certain MTHFR genotype combinations were associated with decreased in utero viability. Mutation analysis revealed that all possible MTHFR genotype combinations were represented in the fetal group, demonstrating that 677T and 1298C alleles could occur in both cis and trans configurations. Combined 677CT/1298CC and 677TT/1298CC genotypes, which contain three and four mutant alleles, respectively, were not observed in the neonatal group (P=.0402). This suggests decreased viability among fetuses carrying these mutations and a possible selection disadvantage among fetuses with increased numbers of mutant MTHFR alleles. This is the first report that describes the existence of human MTHFR 677CT/1298CC and 677TT/1298CC genotypes and demonstrates their potential role in compromised fetal viability.

Abortion, Habitual↗
PubMed2000

Scrapie surveillance in Great Britain: results of an abattoir survey, 1997/98.

A randomised sample of 2,809 apparently healthy sheep, 55 per cent of them less than 15 months of age, which were slaughtered for human consumption at abattoirs in Great Britain in 1997/98, was taken to establish the prevalence of scrapie infection. The medulla oblongata of each sheep was examined histopathologically at the level of the obex, and fresh brain tissue was examined for scrapie-associated fibrils (SAF) to establish whether there was evidence of scrapie. In addition, histological sections of the medulla from 500 of the sheep were immunostained with an antiserum to PrP, and the same technique was also applied to any animal found positive or inconclusive by the histological or SAF examinations. Any sheep which was positive by any of these diagnostic methods was also examined by Western immunoblotting, for the detection of the disease-specific protein PrP(Sc). A total of 2,798 sheep (99.6 per cent) were negative by all the methods applied. Ten animals were SAF-positive but negative by all the other methods, and in one animal there was immunohistochemical staining which could not be interpreted unequivocally as disease-specific. A mathematical model was used to estimate the prevalence of scrapie infection in the national slaughtered sheep population which would be consistent with these results. By this model, the absence of unequivocally substantiated cases of scrapie in the sample was consistent with a prevalence of infection in the slaughter population of up to 11 per cent.

Abattoirs↗
PubMed2000

Effect of hemoglobin levels in hemodialysis patients with asymptomatic cardiomyopathy.

BACKGROUND: Hemoglobin levels below 10 g/dL lead to left ventricular (LV) hypertrophy, LV dilation, a lower quality of life, higher cardiac morbidity, and a higher mortality rate in end-stage renal disease. The benefits and risks of normalizing hemoglobin levels in hemodialysis patients without symptomatic cardiac disease are unknown. METHODS: One hundred forty-six hemodialysis patients with either concentric LV hypertrophy or LV dilation were randomly assigned to receive doses of epoetin alpha designed to achieve hemoglobin levels of 10 or 13.5 g/dL. The study duration was 48 weeks. The primary outcomes were the change in LV mass index in those with concentric LV hypertrophy and the change in cavity volume index in those with LV dilation. RESULTS: In patients with concentric LV hypertrophy, the changes in LV mass index were similar in the normal and low target hemoglobin groups. The changes in cavity volume index were similar in both targets in the LV dilation group. Treatment-received analysis of the concentric LV hypertrophy group showed no correlation between the change in mass index and a correlation between the change in LV volume index and mean hemoglobin level achieved (8 mL/m2 per 1 g/dL hemoglobin decrement, P = 0.009). Mean hemoglobin levels and the changes in LV mass and cavity volume index were not correlated in patients with LV dilation. Normalization of hemoglobin led to improvements in fatigue (P = 0.009), depression (P = 0.02), and relationships (P = 0.004). CONCLUSIONS: Normalization of hemoglobin does not lead to regression of established concentric LV hypertrophy or LV dilation. It may, however, prevent the development of LV dilation, and it leads to improved quality of life.

Adult↗
PubMed2000

Randomized trial of high-flux vs low-flux haemodialysis: effects on homocysteine and lipids.

BACKGROUND: Uncontrolled studies have found that high-flux haemodialysis favourably modifies homocysteine and lipid profiles. We sought to confirm these findings by carrying out a randomized prospective comparison of high-flux and low-flux polysulphone in chronic, stable dialysis patients. METHODS: Forty-eight patients were randomly assigned to either high or low-flux dialysis for 3 months. Serum levels of homocysteine, lipoprotein (a), and lipids were compared between the treatment groups at monthly intervals. RESULTS: All patient characteristics and laboratory variables were equally distributed between the groups at baseline. Over the study duration, we observed no differences between high- and low-flux treatment groups for the following outcomes: pre-dialysis homocysteine, lipoprotein (a), total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides (all P>0.05). Geometric mean (interquartile range) homocysteine at baseline was 20.0 (16.8-24.5) and 19.5 (15.3-22.0) micromol/l for the high-and low-flux groups respectively (P=0.80), and levels did not change significantly during the study. We did demonstrate a more pronounced intradialytic effect of high-flux dialysis on homocysteine levels, which fell during dialysis by 42%, compared to 32% with low-flux dialysis (P<0. 001). CONCLUSIONS: In this randomized controlled trial, the effects of high-flux and low-flux haemodialysis on homocysteine and lipid profiles were comparable. The greater intradialytic effect of high-flux dialysis on homocysteine did not translate into a significant difference in pre-dialysis levels after 3 months of study.

Adult↗
PubMed2000

Adverse outcomes and opioid analgesic administration in acute abdominal pain.

UNLABELLED: To the authors' knowledge, no outcome-based, randomized clinical trial of the safety of opioid analgesics in acute abdominal pain exists. OBJECTIVES: 1) To assess the feasibility of a randomized clinical trial of opioid safety by estimating the adverse outcome rate among patients with abdominal pain severe enough to necessitate opioid analgesics. 2) To explore the association of opioid administration with adverse outcomes in acute abdominal pain. METHODS: The authors conducted a prospective observational study of emergency department (ED) abdominal pain patients, and followed them by telephone at three weeks to determine whether an adverse outcome occurred (defined as obstruction, perforation, ischemia, hemorrhage, peritonitis, sepsis, or death). A logistic regression of factors predicting adverse outcome was performed. RESULTS: Adverse outcomes occurred in 67 of 860 abdominal pain patients (7.8%, 95% CI = 6.1% to 9.8%), and 252 of 860 (29%) received opioids. The adverse outcome rate was 12.7% (95% CI = 9.0% to 17.0%) among patients who received opioids. Variables predictive of adverse outcome in logistic regression included: ED diagnosis of adverse outcome (OR 12.4), age (OR 1.6 per decade), fever (OR 4.6), received opioids (OR 2.1), pain duration (OR 1.5 per day), and leukocytosis (OR 2.0). CONCLUSIONS: A clinical trial would need to randomize more than 1,500 patients to establish the equivalent adverse outcome rates of opioids and placebo: the sample size of all existing studies combined is insufficient to make such a conclusion. Although opioids were associated with a higher adverse outcome rate in this logistic regression, the authors believe this may be due to confounding by pain severity. They emphasize that the study's design precludes conclusion of a causal link. No change in clinical practice is warranted. A randomized clinical trial of sufficient size to definitively resolve this issue is needed.

Abdominal Pain↗
PubMed2000

Preclinical diagnosis of scrapie by immunohistochemistry of third eyelid lymphoid tissue.

Ovine scrapie is a member of the transmissible spongiform encephalopathies (TSEs), a heterogeneous family of fatal neurologic disorders characterized by deposition of an abnormal isoform (prion protein [PrP] PrP-Sc) of a cellular sialoglycoprotein in neural tissue. PrP-Sc is detectable in some lymphoid tissues of infected sheep months or years before development of clinical disease. Detection of PrP-Sc in these tissues is the basis for live-animal testing. In this study, we characterize the performance of a preclinical diagnostic test for ovine scrapie based on a monoclonal antibody (MAb)-based immunohistochemistry assay of nictitating membrane ("third eyelid")-associated lymphoid tissue. The results of third eyelid immunohistochemistry assay agreed with the scrapie status of the sheep for 41 of 42 clinical suspects with confirmed scrapie and 174 of 175 sheep without scrapie. Third eyelid sampling agreed with the scrapie status for 36 of 41 clinically normal sheep positive for PrP-Sc immunostaining of brain tissue, including 27 sheep with positive biopsy specimens that progressed to clinical disease with confirmed scrapie 3 to 20 months after biopsy. The assay used MAb F89/160.1.5, which binds to residues 142 to 145 of ovine PrP. This antibody can be used in combination with MAb F99/97. 6.1, which binds to residues 220 to 225. One or both MAbs in this cocktail recognize PrP sequences conserved in most mammalian species in which natural TSEs have been reported. Immunohistochemistry assay of routinely formalin-fixed lymphoid tissues with a cocktail of pan-specific MAbs is a practical, readily standardized live-animal and preclinical test for ovine scrapie.

Animals↗
PubMed2000

Cardiac arrest witnessed by emergency medical services personnel: descriptive epidemiology, prodromal symptoms, and predictors of survival. OPALS study group.

STUDY OBJECTIVE: The Utstein guidelines recommend that emergency medical services (EMS)-witnessed cardiac arrests be considered separately from other out-of-hospital cardiac arrest cases. The objective of this study was to assess EMS-witnessed cardiac arrest and to determine predictors of survival in this group. METHODS: This prospective cohort included all adults with an EMS-witnessed cardiac arrest in the 21 communities of the Ontario Prehospital Advanced Life Support (OPALS) study. Systems provided a basic life support with defibrillation (BLS-D) level of care. Case and survival definitions followed the Utstein style. Descriptive and univariate methods (chi(2) and t test) were used to characterize EMS-witnessed cardiac arrest. Multivariate logistic regression was undertaken to assess predictors of survival to hospital discharge. RESULTS: From January 1, 1991, to December 31, 1996, there were 9,072 cardiac arrest cases in the study communities. Of these, 610 (6.7%) were EMS-witnessed. The majority had preexisting cardiac or respiratory disease (81.5%) and experienced prodromal symptoms before EMS personnel arrived (91.4%). An initial rhythm of pulseless electrical activity was present in 50.1% of the patients, ventricular fibrillation/ventricular tachycardia in 34.2%, and asystole in 15.7%. Survival to discharge was 12.6%. Multivariate analysis identified the following as independent predictors of survival (odds ratio with 95% confidence intervals [CIs]): nitroglycerin use before EMS arrival: 2.3 (95% CI 1.2 to 4.5), prodromal symptoms of chest pain: 2.5 (95% CI 1.4 to 4.5) or dyspnea: 0.5 (95% CI 0.3 to 1.0), and unconsciousness on EMS arrival: 0.5 (95% CI 0.2 to 0.9). Patients with chest pain were more likely than dyspneic patients to experience ventricular fibrillation/ventricular tachycardia (62% versus 17%, P<.0001), and were 5 times more likely to survive (30.6% versus 6.3%, P<.0001). CONCLUSION: EMS-witnessed cases are clearly an important subset of out-of-hospital cardiac arrest and are characterized by 2 distinct symptom groups: chest pain and dyspnea. These symptoms are important predictors of survival and may also help determine underlying mechanisms before patient collapse. A later phase of the OPALS study will prospectively evaluate the impact of out-of-hospital advanced life support on the survival of victims of EMS-witnessed cardiac arrest.

Adult↗
PubMed1999

Improved out-of-hospital cardiac arrest survival through the inexpensive optimization of an existing defibrillation program: OPALS study phase II. Ontario Prehospital Advanced Life Support.

CONTEXT: Survival rates for out-of-hospital cardiac arrest are low; published survival rates in Ontario are only 2.5%. This study represents phase II of the Ontario Prehospital Advanced Life Support (OPALS) study, which is designed to systematically evaluate the effectiveness and efficiency of various prehospital interventions for patients with cardiac arrest, trauma, and critical illnesses. OBJECTIVE: To assess the impact on out-of-hospital cardiac arrest survival of the implementation of a rapid defibrillation program in a large multicenter emergency medical services (EMS) system with existing basic life support and defibrillation (BLS-D) level of care. DESIGN: Controlled clinical trial comparing survival for 36 months before (phase I) and 12 months after (phase II) system optimization. SETTING: Nineteen urban and suburban Ontario communities (populations ranging from 16 000 to 750 000 [total, 2.7 million]). PATIENTS: All patients who had out-of-hospital cardiac arrest in the study communities for whom resuscitation was attempted by emergency responders. INTERVENTIONS: Study communities optimized their EMS systems to achieve the target response interval from when a call was received until a vehicle stopped with a defibrillator of 8 minutes or less for 90% of cardiac arrest cases. Working both locally and provincially, communities implemented multiple measures, including defibrillation by firefighters, base paging, tiered response agreements with fire departments, continuous quality improvement for response intervals, and province-wide revision and implementation of standard dispatch policies. All response times were obtained from a central dispatch system. MAIN OUTCOME MEASURE: Survival to hospital discharge. RESULTS: The 4690 cardiac arrest patients studied in phase I and the 1641 in phase II were similar for all clinical and demographic characteristics, including age, sex, witnessed status, rhythm, and receipt of bystander cardiopulmonary resuscitation. The proportion of cases meeting the 8-minute response criterion improved (76.7% vs 92.5%; P<.001) as did most median response intervals. Overall survival to hospital discharge for all rhythm groups combined improved from 3.9% to 5.2 % (P = .03). The 33% relative increase in survival represents an additional 21 lives saved each year in the study communities (approximately 1 life per 120000 residents). The charges were estimated to be US $46900 per life saved for establishing the rapid defibrillation program and US $2400 per life saved annually for maintaining the program. CONCLUSION: An inexpensive, multifaceted system optimization approach to rapid defibrillation can lead to significant improvements in survival after cardiac arrest in a large BLS-D EMS system.

Aged↗
PubMed1999

Increased mortality in hemodialyzed patients with elevated serum troponin T: a one-year outcome study.

OBJECTIVES: To determine the significance of elevated serum troponin T (cTnT) occurring in hemodialysis patients in the absence of clinical evidence of acute coronary ischemia. DESIGN AND METHODS: Twelve-month follow-up of cohort of 172 hemodialyzed patients with known serum cTnT concentration. The cohort consisted of patients undergoing hemodialysis in a hospital unit over a 5-month period, with one to four measurements of cTnT. The main outcome measure was death. Cause of death was determined by autopsy in six patients. RESULTS: Of the 31 deaths, 12 were due to acute coronary disease, 14 were noncoronary, and 5 were undefined. Death rates of patients with cTnT <0.1, 0.1-0.2, and >0.2 microg/L were 9.9% (11/111), 32.4% (12/37), and 33.3% (8/24), respectively. The increase in death rate with cTnT > or =0.1 microg/L was significant (p<0.001) for noncoronary deaths, but not for acute coronary deaths. The risk ratios for noncoronary deaths in the subgroups were: nondiabetics 6.6 (95% CI 1.9-23.6), patients with no coronary artery disease 7.3 (1.6-32.4), patients with no peripheral vascular disease 8.9 (2.0-39.7), and hypertensives 9.0 (1.1-76.5). Significant increase in coronary deaths was seen only in patients without hypertension and those aged > or =50 years. The risk ratios for these groups were 9.3 (1.2-74.3) and 3.3 (1.0-10.6), respectively. CONCLUSIONS: Serum cTnT is a potential prognostic marker of mortality in hemodialyzed patient, with increase in death from coronary and noncoronary causes.

Adult↗
PubMed1999

The Ontario Prehospital Advanced Life Support (OPALS) study Part II: Rationale and methodology for trauma and respiratory distress patients. OPALS Study Group.

The Ontario Prehospital Advanced Life Support (OPALS) Study represents the largest prehospital study yet conducted, worldwide. This study will involve more than 25,000 cardiac arrest, trauma, and critically ill patients over an 8-year period (1994-2002). The current article, Part II, describes in detail the rationale and methodology for major trauma and respiratory distress patients and for an economic evaluation of Advanced Life Support (ALS) programs in the OPALS Study. The OPALS Study, using a rigorous controlled methodology and a large sample size, should clearly indicate the benefit in trauma and respiratory distress patient survival and morbidity that results from the widespread introduction of prehospital ALS programs to communities of many different sizes. [Stiell IG, Wells GA, Spaite DW, Nichol G, O'Brien B, Munkley DP, Field BJ, Lyver MB, Luinstra LG, Dagnone E, Campeau T, Ward R, Anderson S, for the OPALS Study Group: The Ontario Prehospital Advanced Life Support (OPALS) Study Part II: Rationale and methodology for trauma and respiratory distress patients.

Emergency Medical Services↗
PubMed1999

Methodologic standards for the development of clinical decision rules in emergency medicine.

The purpose of this review is to present a guide to help readers critically appraise the methodologic quality of an article or articles describing a clinical decision rule. This guide will also be useful to clinical researchers who wish to answer 1 or more questions detailed in this article. We consider the 6 major stages in the development and testing of a new clinical decision rule and discuss a number of standards within each stage. We use examples from emergency medicine and, in particular, examples from our own research on clinical decisions rules for radiography in trauma.

Clinical Trials as Topic↗