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Biomedical subjects

G Wells

Publications and source records attributed to G Wells.

At least 145 records · Page 8Linked to original sources

Octylcyanoacrylate tissue adhesive versus suture wound repair in a contaminated wound model.

BACKGROUND: Octylcyanoacrylate tissue adhesive is a topical wound closure that precludes the need for foreign bodies (sutures) to close wounds. It also has an in vitro antimicrobial effect when standard disc sensitivity tests are used. METHODS: To determine whether contaminated wounds closed with octylcyanoacrylate tissue adhesive will have a lower infection rate compared with wounds closed with 5-0 monofilament sutures, we designed a randomized, blinded, experimental animal study. Two incisions were made on 20 albino guinea pigs. The wounds were contaminated with 10(5) Staphylococcus aureus ATCC 12600 and randomly assigned to be closed with either topical octylcyanoacrylate tissue adhesive or percutaneous 5-0 polypropylene suture. Five days later the adhesive and sutures were removed, and a section of the wound was given to a histopathologist blinded to the type of wound closure. The wound was determined to be infected if inflammatory cells with intracellular cocci were seen. The rest of the wound was opened and examined for clinical evidence of infection. Quantitative bacteriologic analysis was performed. RESULTS: Five wounds in the tissue adhesive group were sterile on day 5, whereas all sutured wounds had positive cultures (25% versus 0%, p < 0.05). Fewer wounds in the tissue adhesive group were determined to be infected by histologic and clinical criteria (0% versus 55%, p < 0.001, and 20% versus 65%, p < 0.01, respectively). Agreement on the determination of infection by histologic and clinical criteria yielded a kappa coefficient of 0.46 (95% confidence interval [GI], 0.19 to 0.73). An infection criterion of 10(5) colony-forming units/gm of tissue correlated poorly with clinical and histologic infection rates (0.19 [95% CI, -0.06 to 0.44] and 0.13 [95% CI, -0.05 to 0.31], respectively). CONCLUSIONS: Contaminated wounds closed with sutures had higher infection rates compared with those reported with topical tissue adhesive. The amount of colonization may not be an accurate method to determine infection.

Animals↗

Differential performance of TRISS-like in early and late blunt trauma deaths.

OBJECTIVES: (1) To independently validate the Trauma and Injury Severity Score-Like (TRISS-Like) model derived by Offner et al. (Revision of TRISS for intubated patients. J Trauma. 1992;32:32-35) in a population of Canadian blunt trauma victims, and (2) to compare the ability of this model to predict mortality in early and late trauma deaths. STUDY POPULATION: Prospective cohort of blunt trauma cases with Injury Severity Score > 12 identified from the Ontario Trauma Registry over a 5-year period. STUDY DESIGN: The TRISS-Like model consisting of age, Injury Severity Score, systolic blood pressure, and best motor response of the Glasgow Coma Scale was evaluated as to its ability to predict mortality by determining the sensitivity, specificity, and the area under the receiver operating characteristic curve. The sample was then divided into early (< or = 7 days) and late mortality subgroups in which model performance was evaluated with respect to time of death. RESULTS: A total of 7,703 patients were included in this analysis. The overall mortality was 12.3%. The TRISS-Like model allowed for assessment of an additional 23% of patients than would standard TRISS and performed with a sensitivity of 97.1%, specificity of 39.8% and an area under the receiver operating characteristic curve of 0.873. Analysis of mortality with respect to time demonstrated that 75% of deaths occurred by day 7. The specificity and receiver operating characteristic area increased in the early (< or = 7 days) subgroup, 46.5% and 0.935, respectively, compared with 20.8% and 0.778 in the late mortality group. CONCLUSIONS: TRISS-Like demonstrated similar performance to that reported with the standard TRISS model but with the additional advantage that it is more generalizable because it can be applied to intubated patients. TRISS-Like demonstrated substantially superior performance in early trauma deaths compared with those that occurred late. This differential performance may be because the model does not include risk factors for late mortality.

Aged↗

Does transfusion practice affect mortality in critically ill patients? Transfusion Requirements in Critical Care (TRICC) Investigators and the Canadian Critical Care Trials Group.

In 4,470 critically ill patients, we examined the impact of transfusion practice on mortality rates. As compared with survivors, patients who died in intensive care units (ICU) had lower hemoglobin values (95 +/- 26 versus 104 +/- 23 g/L, p < 0.0001) and were transfused red cells more frequently (42.6% versus 28.0%, p < 0.0001). In patients with cardiac disease, there was a trend toward an increased mortality when hemoglobin values were < 95 g/L (55% versus 42%, p = 0.09) as compared with anemic patients with other diagnoses. Patients with anemia, a high APACHE II score (> 20), and a cardiac diagnosis had a significantly lower mortality rate when given 1 to 3 or 4 to 6 units of allogeneic red cells (55% [no transfusions] versus 35% [1 to 3 units] or 32% [4 to 6 units], respectively, p = 0.01). Adjusted odds ratio (OR) predicting survival were 0.61 (95% CI; 0.37 to 1.00, p = 0.026) after 1 to 3 units and 0.49 (95% CI; 0.23 to 1.03, p = 0.03) after 4 to 6 units compared with nontransfused anemic patients. In the subgroup with cardiac disease, increasing hemoglobin values in anemic patients was associated with improved survival (OR = 0.80 for each 10 g/L increase, p = 0.012). We conclude that anemia increases the risk of death in critically ill patients with cardiac disease. Blood transfusions appear to decrease this risk.

APACHE↗

Implications of OMERACT outcomes in arthritis and osteoporosis for cochrane metaanalysis.

The Cochrane Collaboration has established a set of methods for pooling multiple studies assessing the same intervention. Assessing the same endpoints in all studies is important to allow different trials to be combined using metaanalysis. OMERACT can play a key role in establishing consensus on the use of common endpoints that are credible to clinicians. We describe the data that need to be included in individual trial reports for metaanalyses to be carried out.

Arthritis↗

Osteoporosis clinical trials endpoints: candidate variables and clinimetric properties.

We reviewed evidence on endpoints used in osteoporosis clinical trials to assist in the development of a set of endpoints to be included in all trials. A MEDLINE search was conducted using the Cochrane Collaboration strategy for each endpoint. Additional published literature was obtained from content experts. A proposed list of endpoints was developed after consultation with experts in the field. Each endpoint was evaluated with respect to validity, reproducibility, redundancy, and feasibility. We classified the endpoints into 2 major categories: clinical health status outcomes and intermediate endpoints, and for each endpoint we present current evidence from the literature as pertains to defined methodologic criteria. Multiple endpoints have been used in osteoporosis clinical trials, and an agreement on a core set of measures needs to be evidence based with an emphasis on validity, reproducibility, and feasibility and to satisfy clinical credibility.

Biomarkers↗

Responsiveness of endpoints in osteoporosis clinical trials.

The usefulness of an endpoint depends in part on its responsiveness to clinically important change. From existing randomized controlled trials, the responsiveness of endpoints currently employed in osteoporosis clinical trials were examined. The responsiveness is presented as the sample size per group needed to show a statistically significant difference. The large variation found means that careful attention needs to be given to the responsiveness of the population studied when estimating the sample size.

Bone Density↗

Macrophage metalloelastase degrades matrix and myelin proteins and processes a tumour necrosis factor-alpha fusion protein.

The matrix metalloproteinases (MMPs) are a group of enzymes which have the ability to degrade extracellular matrix. They also cleave non-matrix proteins such as myelin basic protein and alpha 1-antitrypsin and they are able to process tumour necrosis factor-alpha (TNF) to its mature form. We have cloned, expressed and purified human macrophage metalloelastase (EC 3.4.24.65), an MMP recognised for its ability to degrade elastin, but whose substrate specificity has not yet been defined. With the exception of type I collagen this enzyme degraded all matrix proteins tested, namely: type IV collagen, type I gelatin, fibronectin, laminin, vitronectin and proteoglycan. It also degraded myelin basic protein, cleaved alpha 1-antitrypsin and released TNF from a pro-TNF fusion protein. Thus, in common with several other MMPs, macrophage metalloelastase has a broad substrate range which extends beyond that of elastin alone.

Animals↗

Warfarin for atrial fibrillation. The patient's perspective.

OBJECTIVE: To determine the minimal clinically important difference (MCID) of warfarin therapy for the treatment of nonvalvular atrial fibrillation from the perspective of patients using 2 different elicitation methods. DESIGN: All patients completed 2 face-to-face interviews, which were 2 weeks apart. For each interview, they were randomized to receive 1 of 2 elicitation methods: ping-ponging or starting at the known efficacy. SETTING: The practices of 2 university-affiliated family medicine centers (8 physicians each), 14 community-based family physicians, and 2 cardiologists. PATIENTS: Sixty-four patients with nonvalvular atrial fibrillation who were initiated with warfarin therapy at least 3 months before the study. INTERVENTION: During each interview, the patients' MCIDs were determined by using (1) a pictorial flip chart to describe atrial fibrillation; the consequences of a minor stroke, a major stroke, and a major bleeding episode; the chance of stroke if not taking warfarin; the chance of a major bleeding episode if taking warfarin; examples of the inconvenience, minor side effects, and costs of warfarin therapy; and then (2) 1 of the 2 elicitation methods to determine their MCIDs (the smallest reduction in stroke risk at which the patients were willing to take warfarin). Patients' knowledge of their stroke risk, acceptability of the interview process, and factors determining their preferences were also assessed. MAIN RESULTS: Given a baseline risk of having a stroke in the next 2 years, if not taking warfarin, of 10 of 100, the mean MCID was 2.01 of 100 (95% confidence interval, 1.60-2.42). Fifty-two percent of the patients would take warfarin for an absolute decrease in stroke risk of 1% over 2 years. Before eliciting their MCIDs, patients showed poor knowledge of their stroke risk, which improved afterward. The interview process was well accepted by the patients. The MCID using the ping-ponging elicitation method was 1.015 of 100 smaller compared with use of the starting at the known efficacy method (P = .01). CONCLUSIONS: We were able to determine the MCID of warfarin therapy for the prevention of stroke from the perspective of patients with nonvalvular atrial fibrillation. Their MCIDs were much smaller than those that have been implied by some experts and clinicians. The interview process, using the flip chart approach, appeared to improve the patients' knowledge of their disease and its consequences and treatment. The method used to elicit the patients' MCIDs can have a clinically important effect on patient responses. The method used in our study can be generalized to other conditions and, thus, could be helpful in 3 ways: (1) from a clinical decision-making perspective, it could facilitate patient-physician communication; (2) it could clarify the patient perspective when interpreting the results of previously completed trials; and (3) it could be used to derive more clinically relevant sample sizes for randomized treatment trials.

Aged↗

Formal education and five-year mortality in rheumatoid arthritis: mediation by helplessness scale score.

OBJECTIVE: To analyze scores on a scale designed to measure helplessness, a cognitive variable, as a possible mediator of the association between formal education level and mortality over 5 years in patients with rheumatoid arthritis (RA). METHODS: A cohort of 1,416 patients with RA from 15 private practices in 6 states and Washington, DC was monitored for over 5 years. Demographic, socioeconomic, therapy, functional status, and psychological variables were analyzed as possible predictors of mortality in invariable and multivariable Cox Proportional Hazards models. RESULTS: In a 5-year followup, 1,384 patients were accounted for (97.3%), including 174 who died versus 111 expected (standardized mortality ratio = 1.54). Higher mortality was associated significantly with low formal education, high age, poor scores for activities of daily living (ADL) on a modified health assessment questionnaire (MHAQ), and poor scores on a helplessness scale (all P < 0.01) in univariable analyses. High age, few years of formal education, and poor MHAQ ADL scores were all significant independent predictors of mortality when analyzed simultaneously in a Cox Proportional Hazards model. When helplessness scale scores were included in a model, scores greater than 2.4 (on a scale of 1 to 4), higher age, male gender, and increased MHAQ ADL difficulty scores were all independently significantly predictive of 5-year mortality (P < 0.05), while years of education was no longer a significant predictor. CONCLUSION: Scores on a helplessness scale appear to mediate a component of the association between formal education level and 5-year mortality in these patients with RA. Health professionals and policy makers might consider interventions directed at modification of helplessness as adjunctive to standard interventions to improve outcomes in RA.

Adult↗

Children's emotional and behavioral reactions following the disclosure of extrafamilial sexual abuse: initial effects.

Despite a dramatic increase of the empirical literature on child sexual abuse, very few investigations have examined the initial effects of extrafamilial sexual abuse (ESA). The present study evaluated the emotional and behavioral adjustment of 41 children (mean age 10 years, range 5.4 to 15.5 years) within the first 3 months following the disclosure of ESA. Children's functioning was compared to that of a nonclinical comparison group of 43 children, matched on child's age, gender, and family constellation. Child functioning was assessed using a combination of child-report, primary caregiver-report (i.e., parent), and teacher-report measures. Results revealed that sexually abused children, in comparison to nonabused children, suffered deleterious and clinically significant effects. Standard multiple regressions found that the children's perceptions of self-blame and guilt for the abuse and the extent of traumatization predicted their self-reported symptomatology of depression, social efficacy, and general and abuse-related fears. As well, child's gender predicted the level of general fearfulness. None of the other demographic or abuse-related variables were related to children's functioning. These results underscore the need for multidimensional and multisource assessment of children who experience ESA, and point to the clinical importance of addressing the abuse-related attributions of these children.

Adolescent↗

Secondary traumatization in parents following the disclosure of extrafamilial child sexual abuse: initial effects.

Disclosure or discovery of extrafamilial sexual abuse (ESA) has the potential to traumatize the entire family system. Little controlled research has examined the initial reactions of parents to this type of trauma. The present study evaluated the adjustment of 93 parents (63 mothers and 30 fathers) within 3 months of the disclosure of ESA. Parents' functioning was compared to that of a nonclinical comparison group of 136 parents (74 mothers, 62 fathers). Parent adjustment was assessed using self-report measures of psychological distress, parent competence, family functioning, marital functioning, life stressors, and environmental support. Results revealed that mothers of sexually abused children, in comparison to mothers of nonabused children, experienced greater overall emotional distress, poorer family functioning, and lower satisfaction in their parenting role. Fathers of sexually abused children also experienced greater overall emotional distress relative to comparison fathers but their level of distress remained below that of mothers. Standard and hierarchical multiple regressions on maternal self-reports revealed that mothers' satisfaction with their parenting role and their perceived level of environmental support predicted their emotional functioning. Abuse-related variables did not contribute to the prediction of emotional functioning. These results emphasize the need to expand our focus beyond the child victims to the traumatized families and to normalize the potential for all close family members to be vulnerable to experience adjustment difficulties following ESA.

Adaptation, Psychological↗

Total and functional antibody response to a quadrivalent meningococcal polysaccharide vaccine among children.

OBJECTIVE: To determine total and functional serogroup C antibody response after vaccination with a quadrivalent meningococcal polysaccharide vaccine. DESIGN: Prospective, before and after intervention study. SUBJECTS: Study subjects were between the ages of 0.5 and 19.9 years, and were eligible for a community-wide public health immunization campaign against Neisseria meningitidis serogroup C. METHODS: Total and functional antibody response was measured by enzyme-linked immunosorbent assay and bactericidal assay, respectively. RESULTS: One month after vaccination, total capsular polysaccharide antibody significantly increased in all age groups; a significant rise in bactericidal antibody, that correlated with total capsular polysaccharide antibody, was seen in children 18 months of age and older. At 1 year bactericidal antibody titers were maintained but capsular polysaccharide antibody declined substantially in children younger than 5 years. CONCLUSION: Total capsular polysaccharide antibody concentration appears to be a useful surrogate measure of bactericidal antibody in children 18 months and older. Children who originally received the vaccine at less than 18 months of age should be considered for revaccination if there is a new or continuing risk of disease. Because of the differences in the total and bactericidal antibodies formed, vaccine efficacy trials are required to define which serologic measures are associated with protection.

Adolescent↗

Effectiveness of emergency medical services for victims of out-of-hospital cardiac arrest: a metaanalysis.

STUDY OBJECTIVE: To determine the relative effectiveness of differences in response time interval, proportion of bystander CPR, and type and tier of emergency medical services (EMS) system on survival after out of hospital cardiac arrest. METHODS: We performed a comprehensive literature search, excluding EMS systems other than those of interest (systems of interest were those comprising one tier with providers of basic life support [BLS] or advanced life support [ALS] and those comprising two tiers with providers of BLS or BLS-defibrillation followed by ALS), patient population of fewer than 100 cardiac arrests, studies in which we could not determine the total number of arrests of presumed cardiac origin, and studies lacking data on survival to hospital discharge. Metaanalysis using generalized linear model with dispersion estimation for random effects was then performed. RESULTS: Increased survival to hospital discharge was significantly associated with tier (P < .01), response time interval (P < .01), and bystander CPR (P = .04). A significant interaction was detected between response time interval and bystander CPR (P = .02). For the studies analyzed, survival was 5.2% in a one-tier EMS system or 10.5% in a two-tier EMS system. A 1-minute decrease in mean response time interval was associated with absolute increases in survival rates of .4% and .7% in a one-tier and two-tier EMS systems, respectively. CONCLUSION: Increased survival to hospital discharge may be associated with decreased response time interval and with the use of a two-tier EMS system as opposed to a one-tier system. The data available for this analysis were suboptimal. Policymakers need more methodologically rigorous research to have more reliable and valid estimates of the effectiveness of different EMS systems.

Cardiopulmonary Resuscitation↗

Practice guidelines for the prediction and prevention of pressure ulcers: evaluating the evidence.

Clinical practice guidelines for the prediction and prevention of pressure ulcer (Agency for Health Care Policy and Research [AHCPR], 1992) were evaluated in a Canadian, university-affiliated, acute care hospital. Through a prospective study, the prevalence of pressure ulcers was determined, and pressure ulcer incidence was tracked to evaluate the accuracy of the Braden Scale for risk assessment. The prevalence rate for stage II or greater pressure ulcers was 13.6%; the rate was 29.7% when stage I (persistent redness) was included. In evaluating the Braden Scale's accuracy in predicting risk, the findings from this study were less favorable than previous reports. The total Braden score that appeared to have the best balance of sensitivity (67%) and specificity (66%) was 19. Several factors should be considered: The scale was implemented and tested hospitalwide with a wide range of patient diagnoses, age, and severity; the study was a cross-section of an existing population; and the levels of nursing care and type of staff vary between units ranging from critical to long-term care. This study highlights the need for individual settings to evaluate the AHCPR Guidelines for the Prediction and Prevention of Pressure Ulcers.

Female↗

Can the linguistic interdependence theory support a bilingual-bicultural model of literacy education for deaf students?

Drawing on Cummins' (1989) linguistic interdependence model, proponents of bilingual-bicultural models of literacy education for deaf students claim that, if ASL is well established as the L1, then literacy in English (L2) can be achieved by means of reading and writing without exposure to English through either speech or English-based sign. In our opinion, this claim is based on a false analogy: the situation of the deaf learner of English literacy does not match the conditions assumed by the linguistic interdependence model. We draw on the work of Vygotsky and Halliday to develop a conceptualization of the processes involved in becoming literate, examining the particular and unique challenges that deaf students face as they strive to become members of the linguistic community of users of written English. We argue that becoming literate involves mastering three modes of lanuage use: 'social speech,' 'inner speech,' and written text. In some respects the educational context for deaf students is analogous to that of other bilingual learners; in some crucial aspects, it is very different.

Journal Article↗

Validation of trauma and injury severity score in blunt trauma patients by using a Canadian trauma registry.

OBJECTIVE: To compare outcomes in blunt trauma by using Trauma and Injury Severity Score (TRISS) models derived from the Major Trauma Outcome Study (MTOS) and the Ontario Trauma Registry (OTR) as well as to evaluate the role of the Revised Trauma Score within the TRISS model. METHODS: Consecutive blunt trauma cases from 11 Level I trauma centers over a 4-year period were identified from the OTR. Coefficients of the Revised Trauma Score were modified using the Ontario data and this score was tested by using the Hosmer-Lemeshow Goodness of Fit Test. Two Ontario-specific TRISS models were developed with revised coefficients. The first used the standard Revised Trauma Score and the second used the Revised Trauma Score with regenerated coefficients. The accuracy of mortality predictions for all models were compared by using a Hosmer-Lemeshow Goodness of Fit procedure. Additionally, each TRISS models performance characteristics and receiver operating characteristic (ROC) curves were used to evaluate their discriminative capabilities. RESULTS: A total of 5,436 cases were incorporated in the analysis. Patients with all component TRISS variables had a significantly lower mortality compared to all blunt trauma patients (7.0% vs. 15.5%,p < 0.01). Use of the Revised Trauma Score led to the exclusion of 40% of cases because of absent data necessary to compute the score. The Hosmer-Lemeshow Goodness of Fit statistic for the Revised Trauma Score was 79.45 (p = 0.0001). The Hosmer-Lemeshow Goodness of Fit Statistic ranged from 11.42, p = 0.175 and 13.1, p = 0.125 for the Ontario TRISS models compared to 25.62, p < 0.005 for the MTOS TRISS model. Sensitivity of all three TRISS models ranged from 98% to 99% with specificity ranging from 24% to 35%. ROC curves were identical for all three TRISS models. CONCLUSIONS: TRISS demonstrated satisfactory performance in a Canadian blunt trauma population. Although revision of coefficients led to a better fit on the Hosmer-Lemeshow statistic, ROC curves demonstrated virtually identical performance of the MTOS and Ontario-based TRISS models. The poor performance of the Revised Trauma Score and the observation that its use led to the exclusion of 40% of cases with a higher mortality raises concerns regarding its use in the TRISS model.

Adult↗

Matrix metalloproteinases degrade myelin basic protein.

Matrix metalloproteinases (MMPs) are a group of enzymes responsible for the degradation of interstitial connective tissue and basement membrane. The coding sequences for five of the human MMPs, viz. interstitial collagenase, 72 kDa gelatinase, stromelysin-1, matrilysin and 92 kDa gelatinase, were cloned and expressed in Chinese hamster ovary cells, and the proteins purified. The enzymes were compared for their ability to digest myelin basic protein, the major extrinsic membrane protein of central nervous system myelin. The most active on this substrate was 72 kDa gelatinase, followed by stromelysin-1; interstitial collagenase, matrilysin and 92 kDa gelatinase were of comparable but lesser activity. Production of these enzymes by glia or infiltrating inflammatory cells could therefore contribute to demyelination in neuroinflammatory disease.

Animals↗