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Biomedical subjects

G A Wells

Publications and source records attributed to G A Wells.

At least 91 records · Page 5Linked to original sources

Impact of patient with patient interaction on perceived rheumatoid arthritis overall disease status.

To determine whether patient interaction impacts on perceived disease severity and ability to cope with rheumatoid arthritis (RA) forty RA patients were assessed using joint counts, clinician global assessment, patient global assessment (PGA), VAS pain scale and Health Assessment Questionnaire (HAQ). All participants had six one-on-one conversations about their disease activity and the effect of RA on their lives. Follow-up questionnaires asked about recall of pre-conversation PGA; post-conversation PGA; change in PGA; and change in ability to cope as a result of the conversations. 87.5% of the questionnaires were returned. Pre- and post-conversation PGA were statistically reliable; PGA score improved (P = 0.004); 60.0% of participants felt their ability to cope with their disease improved as a result of this interaction. RA patients benefit from sharing information with like patients. Support groups may be an integral part of treatment strategy in patients with RA.

Arthritis, Rheumatoid↗

A cost effectiveness analysis of cyclosporine in rheumatoid arthritis.

OBJECTIVE: To perform a cost effectiveness analysis of cyclosporine (CyA) in the treatment of rheumatoid arthritis (RA). METHODS: Five randomized controlled parallel group clinical trials were selected for metaanalysis. A fixed effects model was used to calculate the treatment effects among the studies. An incremental economic analysis was performed from both a societal perspective and the perspective of Ontario Ministry of Health (MOH). A placebo comparison and 2 head to head comparisons were performed. The total treatment cost was calculated for a typical patient based on a modified intent to treat approach modelled over a one year period. RESULTS: CyA produced a 25% or greater improvement in tender joint account in 35% of the patients relative to 17% of patients receiving placebo. There was no significant difference in improvement between CyA and azathioprine (Aza) or D-penicillamine (D-Pen). From the perspective of the Ontario MOH, the annual incremental cost of achieving the same level of improvement between CyA and Aza was found to be $1,473, and between CyA and D-Pen, $1,618; the annual incremental cost effectiveness ratio per patient improved of adopting CyA over placebo was $11,547. From a societal perspective, the incremental cost of CyA was $2,886 and $3,731 between Aza and D-Pen, respectively. The annual incremental cost effectiveness ratio against placebo was $20,698. CONCLUSION: Given budgetary constraints on provincial drug plans, guidelines identifying patients in whom the cost effectiveness of CyA may be expected to be most favorable need to be explored. When CyA is the last option available to alleviate RA, whether it is "good value for money" depends upon the importance placed on patient improvement by the patients and/or by society, and on the alternative uses of the same scarce resources.

Antirheumatic Agents↗

Clinical and epidemiological correlates of the neurohistology of cases of histologically unconfirmed, clinically suspect bovine spongiform encephalopathy.

The associations between three major categories of the neurohistological diagnoses and the epidemiological data were examined in unconfirmed cases of clinically suspect bovine spongiform encephalopathy (BSE). The diagnostic categories were focal spongiosis of white matter (37 cases), encephalic listeriosis (13 cases) and no significant lesions (78 cases). An additional control category of 200 confirmed cases of BSE were included for comparison. Epidemiological variables were the frequencies of specific clinical signs, the season of clinical onset, the age, the duration of the clinical signs and the geographical origin of the cases. Discriminant analysis was used to assess the contribution of these variables to the distinction between the diagnostic categories. The analyses characterised the cases of listeriosis by their shortest clinical duration, the greater prevalences of certain clinical signs and their occurrence mainly in winter and spring, consistent with current understanding of the disease. Cases of focal spongiosis, a lesion of unknown significance, but potentially with a metabolic causation, were tentatively separable from cases with no significant lesions by their winter onset. The results also confirmed that among the categories, the cases of BSE had the longest clinical duration. Despite their statistical significance, the findings do not have sufficient predictive power to be of value in making clinical decisions.

Age Distribution↗

Randomized double-blind controlled trial comparing room-temperature and heated lidocaine for digital nerve block.

STUDY OBJECTIVE: To determine whether warming of lidocaine decreases the pain of its injection during digital nerve block. DESIGN: Prospective, randomized, double-blind, controlled trial. INTERVENTIONS: Twenty healthy volunteers received bilateral digital nerve blocks of their middle finger. They were first randomly assigned to receive either room-temperature (21 degrees C) or heated (42 degrees C) 2% lidocaine in their first block. They were then randomly assigned to receive the first block in either the right or left hand. The blocks were performed in a standardized fashion by a single physician, who was blinded to which solution was being used. The volunteers rated the pain of each digital block on a 100-mm visual analog scale (VAS). Efficacy of each digital block was tested at 5 minutes. RESULTS: Heating of the lidocaine was associated with a significantly lower median VAS pain score (31.5 versus 25.0; P < .05). There was no difference in pain score between the two solutions in relation to which hand was used (P = .29) or whether the injection was the first or the second (P = .37). When all factors (temperature, order, and hand) were considered in the ANOVA with respect to VAS pain score, the only significant relation found was that between the temperature of the solution and the VAS pain score (P = .028). CONCLUSION: Heating of lidocaine decreases the pain of injection during digital nerve block.

Adult↗

Derivation of a decision rule for the use of radiography in acute knee injuries.

STUDY OBJECTIVE: To derive a highly sensitive decision rule for the selective use of radiography in acute knee injuries. DESIGN: Prospectively administered survey. SETTING: Emergency departments of two university hospitals. PARTICIPANTS: Convenience sample of 1,047 adults with acute knee injuries. RESULTS: Attending emergency physicians assessed each patient for 23 standardized clinical findings, which were recorded on data collection forms. A total of 127 patients was examined independently by two physicians to determine interobserver agreement. The outcome measure was fracture of the knee. Any patients who did not have ED radiography underwent a structured telephone interview to determine the possibility of a missed fracture. Those variables found to be both reliable (highest kappa values) and strongly associated with a fracture (highest chi 2 values) were further analyzed by a recursive-partitioning multivariate technique. The derived decision rule included the following variables: (1) age 55 years or older, (2) tenderness at the head of the fibula, (3) isolated tenderness of the patella, (4) inability to flex to 90 degrees, and (5) inability to bear weight both immediately and in the ED (four steps). The presence of one or more of these findings would have identified the 68 fractures in the study population with a sensitivity of 1.0 (95% confidence interval [Cl], .95 to 1.0) and a specificity of .54 (95% Cl, .51 to .57). Application of the rule would have led to a 28.0% relative reduction in the use of radiography from 68.6% to 49.4% in the study population. CONCLUSION: A practical, highly sensitive, and reliable decision rule for the use of radiography in acute knee injuries has been derived. Clinical application should await prospective validation of the rule.

Adult↗

Western blot mapping of disease-specific amyloid in various animal species and humans with transmissible spongiform encephalopathies using a high-yield purification method.

SAF-protein, an amyloid, is the main constituent of scrapie-associated fibrils (SAF) and a specific marker for transmissible spongiform encephalopathies (TSE). Using an improved extraction method and Western blot detection, the disease-specific amyloid was found in various parts of the central nervous system of hamsters orally infected with scrapie, of squirrel monkeys orally infected with kuru, sporadic Creutzfeldt-Jakob disease (CJD) and scrapie, of human patients with sporadic CJD, of a sheep with natural scrapie and of a cow with bovine spongiform encephalopathy (BSE). In human CJD samples, the concentration of TSE-specific amyloid was estimated to be 1000- to 10 000-fold lower than in the central nervous system of hamsters with scrapie. The extraction method has a yield of 70% and allows Western blot detection of the TSE-specific amyloid in samples representing 1-10 micrograms of brain tissue from intracerebrally infected hamsters, as well as in individual spleens from hamsters with terminal scrapie infected by the intracerebral, oral or intraperitoneal route. A 20-100 mg sample of material is sufficient for the extraction of the pathological protein from different rodent, monkey, ovine, bovine and human tissues. The results reported here demonstrate the potential suitability of the method for the routine diagnosis of TSE as well as for the detailed analysis of distribution patterns of the TSE-specific amyloid in experimental approaches to the investigation of these diseases.

Amyloid↗

Use of radiography in acute knee injuries: need for clinical decision rules.

OBJECTIVES: To study: 1) the efficiency of the current use of radiography in acute knee injuries, 2) the judgments and attitudes of experienced clinicians in their use of knee radiography, and 3) the potential for decision rules to improve efficiency. METHODS: This two-stage study of adults with acute knee injuries involved: 1) a retrospective review of all 1,967 patients seen over a 12-month period in the EDs of one community and two teaching hospital, and 2) a prospective survey of another 1,040 patients seen by attending emergency physicians. The prospective survey assessed each clinician's estimate of the probability of a knee or patella fracture; 120 patients were independently assessed by two physicians. RESULTS: Of the 1,967 patients seen in the first stage, 74.1% underwent radiography but only 5.2% were found to have fractures. Of the 1,727 knee and patella radiographic series ordered, 92.4% were negative for fracture. In the second stage, experienced physicians predicted the probability of fracture to be 0 or 0.1 for 75.6% of the patients. The kappa value for this response was 0.51 (95% CI 0.34 to 0.68). The physicians also indicated that they would have been comfortable or very comfortable in not ordering radiography for 55.5% of the patients. The area under the receiver operating characteristics curve for the physicians' prediction of fracture was 0.87 (95% CI 0.82 to 0.91), reflecting good discrimination between fracture and nonfracture cases. Likelihood ratios for the physicians' prediction ranged from 0.09 at the 0 level to 42.9 at the 0.9-1.0 level. CONCLUSIONS: Emergency physicians order radiography for most patients with acute knee injuries, even though they can accurately discriminate between fracture and nonfracture cases and expect most of the radiographs to be normal. These findings suggest great potential for more efficient use of knee radiography, possibly through the use of a clinical decision rule.

Adolescent↗

Association of drug therapy with survival in cardiac arrest: limited role of advanced cardiac life support drugs.

OBJECTIVE: To generate hypotheses regarding the association of standard Advanced Cardiac Life Support (ACLS) drugs with human cardiac arrest survival. METHODS: This observational cohort study was conducted over a two-year period in the wards, intensive care units, and EDs of two tertiary care hospitals. Included werc adult patients who suffered cardiac arrest either inside or outside the hospital and who required epinephrine according to standard ACLS guidelines. Six standard ACLS drugs (given while CPR was in progress) were assessed for association with survival from resuscitation to one hour and to hospital discharge by univariate and multivariate logistic regression analyses. RESULTS: In the 529 patients studied, initial cardiac rhythm had no impact on the association between drug administration and survival. The time of drug administration (quartile of ACLS period) was associated with resuscitation for atropine (p < 0.05) and lidocaine (p < 0.01). The odds ratios (95% CIs) for successful resuscitation, after multivariate adjustment for potential confounders, were: a respiratory initiating cause, 3.7 (2.1 -6.4); each 5-minute increase in CPR-ACLS interval, 0.5 (0.4-0.7); each 5-minute duration of ACLS. 0.9 (()1.8- 1.0; atropine, 1.2 (1.0-1.3); bretylium. (0.4 (0.1-1.1); calcium 0.8 (0.2-2.4); lidocaine, 0.9 (0.7-1.1); procainamide. 21.0 (5.2-84.0) d sodium bicarbonate 1.2 (1.0-1.6). All other potential confounding variables entered into the model were not significantly associated with resuscitation. CONCLUSION: Initiating cause of arrest, time to ACLS, and duration of ACLS were important correlates of survival. Other than procainaimide, standard ACLS drugs had relatively little association with survival, but timing of administration may be an important factor. Further research using definitive large randomized controlled trials is warranted to assess the role of drug therapy in improving cardiac arrest survival.

Adult↗

The neuropathology and epidemiology of bovine spongiform encephalopathy.

Bovine spongiform encephalopathy (BSE), defined originally from its characteristic neuropathology, retains a place of particular interest in the scrapie-like or prion disease group, presenting uniquely an example of such diseases occurring as a nationwide food-borne epidemic in Great Britain. Comprehensive monitoring of the epidemic, both pathologically and epidemiologically, has facilitated our present understanding of the disease. BSE presents the classical neuropathological features of the transmissible spongiform encephalopathies. Although particularly similar to natural scrapie of sheep, BSE has, unlike scrapie, a stereotypic lesion profile from which it has been concluded that host and agent factors, including probably the strain of agent, which influence the profile, are constant in this disease. Neuronal loss in BSE may make an important but hitherto inapparent contribution to functional deficits. Preliminary ultrastructural studies have confirmed light microscopic features of brain changes in BSE but have as yet not established significant new findings. Immunohistochemical studies of PrP accumulation reveal distinctive forms and distributions of immunolabelling, confirming features reported previously in experimental models of scrapie, including perineuronal and perineuritic "synapse-like" reactivity. The histopathological diagnosis of BSE, validated on a single section of the medulla for the statutory diagnosis of large numbers of cases, is supplemented where necessary by fibril (SAF) examination which performs similarly to the histological diagnosis in the majority of cases. Epidemiological studies of BSE have supported the pathological findings that there is no detectable variation in susceptibility within the cattle population. The detailed monitoring of the epidemic has revealed the expected effects on the incidence as a result of statutory measures intended to prevent food-borne exposure after July 1988. The main effect has been a reduction in the national incidence during 1993 which has been continued into 1994. Analytical studies have not revealed any means of transmission, other than the food-borne source, capable of maintaining the epidemic in Great Britain. An international comparison of risk factors for the occurrence of BSE indicates that an epidemic of similar magnitude outside the British Isles is unlikely.

Animals↗

Statistical power, sample size, and their reporting in randomized controlled trials.

OBJECTIVE: To describe the pattern over time in the level of statistical power and the reporting of sample size calculations in published randomized controlled trials (RCTs) with negative results. DESIGN: Our study was a descriptive survey. Power to detect 25% and 50% relative differences was calculated for the subset of trials with negative results in which a simple two-group parallel design was used. Criteria were developed both to classify trial results as positive or negative and to identify the primary outcomes. Power calculations were based on results from the primary outcomes reported in the trials. POPULATION: We reviewed all 383 RCTs published in JAMA, Lancet, and the New England Journal of Medicine in 1975, 1980, 1985, and 1990. RESULTS: Twenty-seven percent of the 383 RCTs (n = 102) were classified as having negative results. The number of published RCTs more than doubled from 1975 to 1990, with the proportion of trials with negative results remaining fairly stable. Of the simple two-group parallel design trials having negative results with dichotomous or continuous primary outcomes (n = 70), only 16% and 36% had sufficient statistical power (80%) to detect a 25% or 50% relative difference, respectively. These percentages did not consistently increase over time. Overall, only 32% of the trials with negative results reported sample size calculations, but the percentage doing so has improved over time from 0% in 1975 to 43% in 1990. Only 20 of the 102 reports made any statement related to the clinical significance of the observed differences. CONCLUSIONS: Most trials with negative results did not have large enough sample sizes to detect a 25% or a 50% relative difference. This result has not changed over time. Few trials discussed whether the observed differences were clinically important. There are important reasons to change this practice. The reporting of statistical power and sample size also needs to be improved.

Publishing↗

Implementation of the Ottawa ankle rules.

OBJECTIVE: To assess the impact on clinical practice of implementing the Ottawa ankle rules. DESIGN: Nonrandomized, controlled trial with before-after and concurrent controls. SETTING: Emergency departments of a university (intervention) hospital and a community (control) hospital. PATIENTS: All 2342 adults seen with acute ankle injuries during 5-month periods before and after the intervention. INTERVENTION: The implementation of the Ottawa ankle rules by emergency department physicians. MAIN OUTCOME MEASURE: Proportions of patients referred for standard ankle and foot radiographic series. RESULTS: There was a relative reduction in ankle radiography by 28% at the intervention hospital but an increase by 2% at the control hospital (P < .001). Foot radiography was reduced by 14% at the intervention hospital but increased by 13% at the control hospital (P < .05). Compared with nonfracture patients who had radiography during the after period at the intervention hospital, those discharged without radiography spent less time in the emergency department (80 minutes vs 116 minutes; P < .0001), had lower estimated total medical costs for physician visits and radiography ($62 vs $173; P < .001), but did not differ in the proportion satisfied with emergency physician care (95% vs 96%) or undergoing subsequent radiography (5% vs 5%). The rules were found to have sensitivities of 1.0 (95% confidence interval [CI], 0.95 to 1.0) for detecting 74 malleolar fractures and 1.0 (95% CI, 0.82 to 1.0) for detecting 19 midfoot fractures. In the following 12 months at the intervention hospital, use of radiography did not increase. CONCLUSIONS: Implementation of the Ottawa ankle rules led to a decrease in use of ankle radiography, waiting times, and costs without patient dissatisfaction or missed fractures. Future studies should address the generalizability of these decision rules in a variety of hospital settings.

Adult↗