Biomedical subjects

G A Wells

Publications and source records attributed to G A Wells.

At least 19 recordsLinked to original sources

PubMed2006

Strontium ranelate for preventing and treating postmenopausal osteoporosis.

BACKGROUND: Strontium ranelate is a new treatment for osteoporosis therefore, its benefits and harms need to be known. OBJECTIVES: To determine the efficacy and safety of strontium ranelate for the treatment and prevention of postmenopausal osteoporosis. SEARCH STRATEGY: We searched MEDLINE (1996 to March 2005), EMBASE (1996 to week 9 2005), the Cochrane Library (1996 to Issue 1 2005), reference lists of relevant articles and conference proceedings from the last two years. Additional data was sought from authors. SELECTION CRITERIA: We included randomized controlled trials (RCTs) of at least one year duration comparing strontium ranelate versus placebo reporting fracture incidence, bone mineral density (BMD), health related quality of life or safety in postmenopausal women. Treatment (versus prevention) population was defined as women with prevalent vertebral fractures and/or lumbar spine BMD T score < -2.5 SD. DATA COLLECTION AND ANALYSIS: Two reviewers independently determined study eligibility, assessed trial quality and extracted the relevant data. Disagreements were resolved by consensus. RCTs were grouped by dose of strontium ranelate and treatment duration. Where possible, meta-analysis was conducted using the random effects model. MAIN RESULTS: Four trials met the inclusion criteria. Three included a treatment population (0.5 to 2 g of strontium ranelate daily) and one a prevention population (0.125 g, 0.5 g and 1 g daily). A 37% reduction in vertebral fractures (RR 0.63, 95% CI 0.56, 0.71) and a 14% reduction in non-vertebral fractures (RR 0.86, 95% CI 0.75, 0.98) were demonstrated over three years with 2 g of strontium ranelate daily in a treatment population. An increase in BMD was shown at all BMD sites after two to three years in both populations. Lower doses of strontium ranelate were superior to placebo and the highest dose demonstrated the greatest reduction in vertebral fractures and increase in BMD. An increased risk of diarrhea with 2 g of strontium ranelate was found; however, adverse events did not affect the risk of discontinuing treatment nor did it increase the risk of serious side effects, gastritis or death. Additional data suggests that the risk of vascular and nervous system side-effects is slightly increased with taking 2 g of strontium ranelate daily over three to four years. AUTHORS' CONCLUSIONS: There is silver level evidence (www.cochranemsk.org) to support the efficacy of strontium ranelate for the reduction of fractures (vertebral and to a lesser extent non-vertebral) in postmenopausal osteoporotic women and an increase in BMD in postmenopausal women with/without osteoporosis. Diarrhea may occur however, adverse events leading to study withdrawal were not significantly increased with taking 2 g of strontium ranelate daily. Potential vascular and neurological side-effects need to be further explored.

Bone Density↗

PubMed2006

Strontium ranelate for preventing and treating postmenopausal osteoporosis.

BACKGROUND: Strontium ranelate is a new anti-osteoporosis therapy therefore, its benefits and harms need to be known. OBJECTIVES: To determine the efficacy and safety of strontium ranelate for the treatment and prevention of postmenopausal osteoporosis. SEARCH STRATEGY: We searched MEDLINE (1996 to March 2005), EMBASE (1996 to week 9 2005), the Cochrane Library (1996 to Issue 1 2005), reference lists of relevant articles and conference proceedings from the last two years. Additional data was sought from authors and industry sponsors. SELECTION CRITERIA: We included randomized controlled trials (RCTs) of at least one year duration comparing strontium ranelate versus placebo reporting fracture incidence, bone mineral density (BMD), health related quality of life and/or safety outcomes in postmenopausal women. Treatment (versus prevention) population was defined as women with prevalent vertebral fractures and/or lumbar spine BMD T score < -2.5 SD. DATA COLLECTION AND ANALYSIS: Two reviewers independently determined study eligibility, assessed trial quality and extracted the relevant data. Disagreements were resolved by consensus. RCTs were grouped by dose of strontium ranelate and treatment duration. Where possible, meta-analysis was conducted using the random effects model. MAIN RESULTS: A total of four trials met our inclusion criteria, three of which investigated the effects of strontium ranelate compared to placebo in a treatment population (doses ranged from 0.5 to 2 g daily) and one, in a prevention population (doses 0.125, 0.5 and 1 g daily). In osteoporotic, postmenopausal women a 37% reduction in vertebral fractures (two trials, n = 5082, RR 0.63, 95% CI 0.56 to 0.71) and a 14% reduction in non-vertebral fractures (two trials, n = 6572, RR 0.86, 95% CI 0.75 to 0.98) was demonstrated over a three year period with 2 g of strontium ranelate daily. An increase in BMD at all sites was shown with the same dose: lumbar spine BMD (two trials, n = 1614, WMD adjusted for strontium content 5.44, 95% CI 3.41 to 7.46 and WMD not adjusted 11.29, 95% CI 10.22 to 12.37 over two years), femoral neck and total hip (two trials, n = 4230, WMD 8.25, 95% CI 7.84 to 8.66 and WMD 9.83, 95% CI 9.39 to 10.26 respectively over three years). One gram of strontium ranelate daily in postmenopausal women without osteoporosis increased BMD at all sites over a two year period: lumbar spine (one trial, n = 59, WMD adjusted for strontium content 2.39, 95% CI 0.15 to 4.63 and WMD not adjusted 6.68, 95% CI 5.16 to 8.20), femoral neck (one trial, n= 60, WMD 2.52, 95%CI 0.96 to 4.09) and total hip (one trial, n = 60, WMD 1.02, 95% CI 0.48 to 1.56). In both the treatment and prevention populations, lower doses of strontium ranelate were superior to placebo with the highest dose of strontium ranelate demonstrating the greatest reduction in vertebral fractures and increase in BMD. There is some evidence to suggest that 2 g of strontium ranelate daily compared to placebo may have a beneficial effect on health related quality of life in postmenopausal women after three years of treatment. Two grams of strontium ranelate daily increased the risk of diarrhea (RR 1.38%, 95% CI 1.02 to 1.87); however, adverse events did not affect the risk of discontinuing strontium ranelate nor did it increase the risk of serious side effects, gastritis or death. Additional data obtained suggests that the risk of vascular system disorders including venous thromboembolism (two trials, n = 6669, 2.2% versus 1.5%, OR 1.5, 95% CI 1.1 to 2.1) and pulmonary embolism (two trials, n = 6669, 0.8% versus 0.4%, OR 1.7, 95% CI 1.0 to 3.1) as well as nervous system disorders such as headaches (3.9% versus 2.9%), seizures (0.3% versus 0.1%), memory loss (2.4% versus 1.9%) and disturbance in consciousness (2.5% versus 2.0%) is slightly increased with taking 2 g of strontium ranelate daily over a 3 to 4 year period. AUTHORS' CONCLUSIONS: There is silver level evidence to support the efficacy of strontium ranelate for the reduction of vertebral fractures (and to a lesser extent non-vertebral fractures) in postmenopausal osteoporotic women and an increase in BMD (all sites) in postmenopausal women with and without osteoporosis. Diarrhea may occur however, adverse events leading to study withdrawal were not significantly increased in the strontium ranelate group. Potential risks to the vascular and neurological system associated with taking 2 g of strontium ranelate daily need to be further explored and quantified.

Bone Density↗

PubMed2004

Prophylactic antibiotics for abdominal hysterectomy: indication for low-risk Canadian women.

OBJECTIVE: To determine whether prophylactic antibiotics decrease the risk of infectious morbidity after total abdominal hysterectomy (TAH) in women at low risk for infection. METHODS: An analysis of data from 1570 women undergoing planned TAH at 15 secondary and tertiary hospitals in Nova Scotia, Ontario, and Quebec, who agreed to participate in a centrally randomized controlled trial of vaginal antisepsis with povidone-iodine gel compared to no gel after the standard preoperative vaginal preparation with povidone-iodine solution. RESULTS: Prophylactic antibiotics were used in 993 of 1570 women (63%). Appropriately timed prophylactic antibiotics decreased infectious morbidity (odds ratio [OR], 0.65; 95% confidence interval [CI], 0.50-0.85; P < .002). After controlling for risk factors for infection and study centre, the protective effect was even more pronounced (adjusted OR, 0.51; 95% CI, 0.36-0.73). Prophylactic antibiotics were associated with decreases in abdominal wound infection (OR, 0.45; 95% CI, 0.30-0.66) and pelvic infection (OR, 0.49; 95% CI, 0.26-0.92). CONCLUSION: Women who did not receive prophylactic antibiotics had a higher surgical infection rate. Prophylactic antibiotics should be recommended for all women undergoing TAH.

Anti-Infective Agents, Local↗

PubMed2003

Cost effectiveness of defibrillation by targeted responders in public settings.

BACKGROUND: Out-of-hospital cardiac arrest is frequent and has poor outcomes. Defibrillation by trained targeted nontraditional responders improves survival versus historical controls, but it is unclear whether such defibrillation is a good value for the money. Therefore, this study estimated the incremental cost effectiveness of defibrillation by targeted nontraditional responders in public settings by using decision analysis. METHODS AND RESULTS: A Markov model evaluated the potential cost effectiveness of standard emergency medical services (EMS) versus targeted nontraditional responders. Standard EMS included first-responder defibrillation followed by advanced life support. Targeted nontraditional responders included standard EMS supplemented by defibrillation by trained lay responders. The analysis adopted a US societal perspective. Input data were derived from published or publicly available data. Future costs and effects were discounted at 3%. Monte Carlo simulation and sensitivity analyses assessed the robustness of results. Standard EMS had a median of 0.47 (interquartile range [IQR]=0.32 to 0.69) quality-adjusted life years and a median of 14 100 dollars (IQR=8600 dollars to 21 900 dollars) costs per arrest. Targeted nontraditional responders in casinos had an incremental cost of a median 56 700 dollars (IQR=44 100 dollars to 77 200 dollars) per additional quality-adjusted life year. The results were sensitive to changes in time to defibrillation, incidence of arrest, and number of devices required to implement rapid defibrillation. CONCLUSIONS: Where cardiac arrest is frequent and response time intervals are short, rapid defibrillation by targeted nontraditional responders may be a good value for the money compared with standard EMS. The incidence of arrest should be considered when choosing locations to implement public access defibrillation.

Adult↗

PubMed2003

Meta-analysis of the effect of structured exercise training on cardiorespiratory fitness in Type 2 diabetes mellitus.

AIMS/HYPOTHESIS: Low cardiorespiratory fitness is a powerful and independent predictor of mortality in people with diabetes. Several studies have examined the effects of exercise on cardiorespiratory fitness in Type 2 diabetic individuals. However, these studies had relatively small sample sizes and highly variable results. Therefore the aim of this study was to systematically review and quantify the effects of exercise on cardiorespiratory fitness in Type 2 diabetic individuals. METHODS: MEDLINE, EMBASE, and four other databases were searched up to March 2002 for randomized, controlled trials evaluating effects of structured aerobic exercise interventions of 8 weeks or more on cardiorespiratory fitness in adults with Type 2 diabetes. Cardiorespiratory fitness was defined as maximal oxygen uptake (VO(2max)) during a maximal exercise test. RESULTS: Seven studies, presenting data for nine randomized trials comparing exercise and control groups (overall n=266), met the inclusion criteria. Mean exercise characteristics were as follows: 3.4 sessions per week, 49 min per session for 20 weeks. Exercise intensity ranged from 50% to 75% of VO(2max). There was an 11.8% increase in VO(2max) in the exercise group and a 1.0% decrease in the control group (post intervention standardized mean difference =0.53, p<0.003). Studies with higher exercise intensities tended to produce larger improvements in VO(2max). Exercise intensity predicted post-intervention weighted mean difference in HbA(1c) (r=-0.91, p=0.002) to a larger extent than did exercise volume (r=-0.46, p=0.26). CONCLUSIONS/INTERPRETATION: Regular exercise has a statistically and clinically significant effect on VO(2max) in Type 2 diabetic individuals. Higher intensity exercise could have additional benefits on cardiorespiratory fitness and HbA(1c).

Databases, Factual↗

PubMed2003

Number needed to treat (NNT): implication in rheumatology clinical practice.

OBJECTIVE: To calculate the number needed to treat (NNT) and number needed to harm (NNH) from the data in rheumatology clinical trials and systematic reviews. METHODS: The NNTs for the clinically important outcome measures in the rheumatology systematic reviews from the Cochrane Library, issue 2, 2000 and in the original randomised, double blind, controlled trials were calculated. The measure used for calculating the NNT in rheumatoid arthritis (RA) interventions was the American College of Rheumatology 20% improvement or Paulus criteria; in osteoarthritis (OA) interventions, the improvement of pain; and in systemic sclerosis (SSc) interventions, the improvement of Raynaud's phenomenon. The NNH was calculated from the rate of withdrawals due to adverse events from the treatment. RESULTS: The data required for the calculation of the NNT were available in 15 systematic reviews and 11 original articles. For RA interventions, etanercept treatment for six months had the smallest NNT (1.6; 95% confidence interval (CI) 1.4 to 2.0), whereas leflunomide had the largest NNH (9.6; 95% CI 6.8 to 16.7). For OA treatment options, only etodolac and tenoxicam produced significant pain relief compared with placebo (NNT=4.4; 95% CI 2.4 to 24.4 and 3.8; 95% CI 2.5 to 7.3, respectively). For SSc interventions, none were shown to be efficacious in improving Raynaud's phenomenon because the 95% CI of the NNT was infinite. CONCLUSIONS: The NNT and NNH are helpful for clinicians, enabling them to translate the results from clinical trials and systematic reviews to use in routine clinical practice. Both NNT and NNH should be accompanied by a limited 95% CI and adjusted for the individual subject's baseline risk.

Antirheumatic Agents↗

PubMed2001

Rapid test for the preclinical postmortem diagnosis of BSE in central nervous system tissue.

The efficacy of a rapid test for detecting PrP(Sc) in central nervous system tissue was evaluated for the postmortem diagnosis of BSE at different times during the course of the disease. One hundred and six samples of brain, at the level of the medulla oblongata, and spinal cord, derived from the experimental study of the pathogenesis of BSE carried out in Great Britain between 1991 and 1995, were examined. PrP(Sc) was detected in the samples from most of the exposed animals killed 32 months or more after they had been exposed to the agent, and before the onset of clinical signs which were first recorded at 35 months. Comparisons with the results of histology, fibril detection, PrP immunohistochemistry and mouse bioassay indicated that the rapid test is at least as sensitive as these conventional confirmatory diagnostic methods and its result can be obtained more quickly.

Animals↗

PubMed2001

The Canadian C-spine rule for radiography in alert and stable trauma patients.

CONTEXT: High levels of variation and inefficiency exist in current clinical practice regarding use of cervical spine (C-spine) radiography in alert and stable trauma patients. OBJECTIVE: To derive a clinical decision rule that is highly sensitive for detecting acute C-spine injury and will allow emergency department (ED) physicians to be more selective in use of radiography in alert and stable trauma patients. DESIGN: Prospective cohort study conducted from October 1996 to April 1999, in which physicians evaluated patients for 20 standardized clinical findings prior to radiography. In some cases, a second physician performed independent interobserver assessments. SETTING: Ten EDs in large Canadian community and university hospitals. PATIENTS: Convenience sample of 8924 adults (mean age, 37 years) who presented to the ED with blunt trauma to the head/neck, stable vital signs, and a Glasgow Coma Scale score of 15. MAIN OUTCOME MEASURE: Clinically important C-spine injury, evaluated by plain radiography, computed tomography, and a structured follow-up telephone interview. The clinical decision rule was derived using the kappa coefficient, logistic regression analysis, and chi(2) recursive partitioning techniques. RESULTS: Among the study sample, 151 (1.7%) had important C-spine injury. The resultant model and final Canadian C-Spine Rule comprises 3 main questions: (1) is there any high-risk factor present that mandates radiography (ie, age >/=65 years, dangerous mechanism, or paresthesias in extremities)? (2) is there any low-risk factor present that allows safe assessment of range of motion (ie, simple rear-end motor vehicle collision, sitting position in ED, ambulatory at any time since injury, delayed onset of neck pain, or absence of midline C-spine tenderness)? and (3) is the patient able to actively rotate neck 45 degrees to the left and right? By cross-validation, this rule had 100% sensitivity (95% confidence interval [CI], 98%-100%) and 42.5% specificity (95% CI, 40%-44%) for identifying 151 clinically important C-spine injuries. The potential radiography ordering rate would be 58.2%. CONCLUSION: We have derived the Canadian C-Spine Rule, a highly sensitive decision rule for use of C-spine radiography in alert and stable trauma patients. If prospectively validated in other cohorts, this rule has the potential to significantly reduce practice variation and inefficiency in ED use of C-spine radiography.

Adult↗

PubMed2001

Neuroprotective effect of mild hypothermia in patients undergoing coronary artery surgery with cardiopulmonary bypass: a randomized trial.

BACKGROUND: Neuropsychological deficits occur in 30% to 80% of patients undergoing heart surgery and are due in part to ischemic cerebral injury during cardiopulmonary bypass. We tested whether mild hypothermia, the most efficacious neuroprotective strategy found in laboratory studies, improved cognitive outcome in patients undergoing coronary artery surgery. METHODS AND RESULTS: Patients 60 years or older scheduled for coronary artery surgery were enrolled. During cardiopulmonary bypass, patients were initially cooled to 32 degrees C then randomly assigned to rewarming to 37 degrees C (control) or 34 degrees C (hypothermic), with no further intraoperative warming. Testing was scheduled preoperatively and 1 week and 3 months postoperatively. Eleven tests were combined into 3 cognitive domains: memory, attention, and psychomotor speed and dexterity. A patient was classified as having a cognitive deficit if a decrease of >/=0.50 SD was realized in 1 or more domains. The incidence of cognitive deficits 1 week after surgery, which was the primary outcome, was 62% () in the control group and 48% () in the hypothermic group (relative risk 0.77, P=0.048). In the hypothermic group, the magnitude of deterioration in attention and in speed and dexterity was reduced by 55.6% (P=0.038) and 41.3% (P=0.042), respectively. At 3 months, the hypothermic group still performed better on one test of speed and dexterity (grooved pegboard). There was no difference in morbidity or mortality. CONCLUSIONS: Our findings support a neuroprotective effect of mild hypothermia in patients undergoing coronary artery surgery and should encourage physicians and perfusionists to pay careful attention to brain temperature during cardiopulmonary bypass.

Aged↗

PubMed2001

Effects of exercise on glycemic control and body mass in type 2 diabetes mellitus: a meta-analysis of controlled clinical trials.

CONTEXT: Exercise is widely perceived to be beneficial for glycemic control and weight loss in patients with type 2 diabetes. However, clinical trials on the effects of exercise in patients with type 2 diabetes have had small sample sizes and conflicting results. OBJECTIVE: To systematically review and quantify the effect of exercise on glycosylated hemoglobin (HbA(1c)) and body mass in patients with type 2 diabetes. DATA SOURCES: Database searches of MEDLINE, EMBASE, Sport Discuss, Health Star, Dissertation Abstracts, and the Cochrane Controlled Trials Register for the period up to and including December 2000. Additional data sources included bibliographies of textbooks and articles identified by the database searches. STUDY SELECTION: We selected studies that evaluated the effects of exercise interventions (duration >/=8 weeks) in adults with type 2 diabetes. Fourteen (11 randomized and 3 nonrandomized) controlled trials were included. Studies that included drug cointerventions were excluded. DATA EXTRACTION: Two reviewers independently extracted baseline and postintervention means and SDs for the intervention and control groups. The characteristics of the exercise interventions and the methodological quality of the trials were also extracted. DATA SYNTHESIS: Twelve aerobic training studies (mean [SD], 3.4 [0.9] times/week for 18 [15] weeks) and 2 resistance training studies (mean [SD], 10 [0.7] exercises, 2.5 [0.7] sets, 13 [0.7] repetitions, 2.5 [0.4] times/week for 15 [10] weeks) were included in the analyses. The weighted mean postintervention HbA(1c) was lower in the exercise groups compared with the control groups (7.65% vs 8.31%; weighted mean difference, -0.66%; P<.001). The difference in postintervention body mass between exercise groups and control groups was not significant (83.02 kg vs 82.48 kg; weighted mean difference, 0.54; P =.76). CONCLUSION: Exercise training reduces HbA(1c) by an amount that should decrease the risk of diabetic complications, but no significantly greater change in body mass was found when exercise groups were compared with control groups.

Adult↗

PubMed2001

Vasopressin versus epinephrine for inhospital cardiac arrest: a randomised controlled trial.

BACKGROUND: Survival rates for cardiac arrest patients, both in and out of hospital, are poor. Results of a previous study suggest better outcomes for patients treated with vasopressin than for those given epinephrine, in the out-of-hospital setting. Our aim was to compare the effectiveness and safety of these drugs for the treatment of in-patient cardiac arrest. METHODS: We did a triple-blind randomised trial in the emergency departments, critical care units, and wards of three Canadian teaching hospitals. We assigned adults who had cardiac arrest and required drug therapy to receive one dose of vasopressin 40 U or epinephrine 1 mg intravenously, as the initial vasopressor. Patients who failed to respond to the study intervention were given epinephrine as a rescue medication. The primary outcomes were survival to hospital discharge, survival to 1 h, and neurological function. Preplanned subgroup assessments included patients with myocardial ischaemia or infarction, initial cardiac rhythm, and age. FINDINGS: We assigned 104 patients to vasopressin and 96 to epinephrine. For patients receiving vasopressin or epinephrine survival did not differ for hospital discharge (12 [12%] vs 13 [14%], respectively; p50.67; 95% CI for absolute increase in survival 211.8% to 7.8%) or for 1 h survival (40 [39%] vs 34 [35%]; p50.66; 210.9% to 17.0%); survivors had closely similar median mini-mental state examination scores (36 [range 19-38] vs 35 [20-40]; p50.75) and median cerebral performance category scores (1 vs 1). INTERPRETATION: We failed to detect any survival advantage for vasopressin over epinephrine. We cannot recommend the routine use of vasopressin for inhospital cardiac arrest patients, and disagree with American Heart Association guidelines, which recommend vasopressin as alternative therapy for cardiac arrest.

Aged↗

PubMed2001

The Canadian CT Head Rule for patients with minor head injury.

BACKGROUND: There is much controversy about the use of computed tomography (CT) for patients with minor head injury. We aimed to develop a highly sensitive clinical decision rule for use of CT in patients with minor head injuries. METHODS: We carried out this prospective cohort study in the emergency departments of ten large Canadian hospitals and included consecutive adults who presented with a Glasgow Coma Scale (GCS) score of 13-15 after head injury. We did standardised clinical assessments before the CT scan. The main outcome measures were need for neurological intervention and clinically important brain injury on CT. FINDINGS: The 3121 patients had the following characteristics: mean age 38.7 years); GCS scores of 13 (3.5%), 14 (16.7%), 15 (79.8%); 8% had clinically important brain injury; and 1% required neurological intervention. We derived a CT head rule which consists of five high-risk factors (failure to reach GCS of 15 within 2 h, suspected open skull fracture, any sign of basal skull fracture, vomiting >2 episodes, or age >65 years) and two additional medium-risk factors (amnesia before impact >30 min and dangerous mechanism of injury). The high-risk factors were 100% sensitive (95% CI 92-100%) for predicting need for neurological intervention, and would require only 32% of patients to undergo CT. The medium-risk factors were 98.4% sensitive (95% CI 96-99%) and 49.6% specific for predicting clinically important brain injury, and would require only 54% of patients to undergo CT. INTERPRETATION: We have developed the Canadian CT Head Rule, a highly sensitive decision rule for use of CT. This rule has the potential to significantly standardise and improve the emergency management of patients with minor head injury.

Adolescent↗

PubMed2001

Inconsistent detection of PrP in extraneural tissues of cats with feline spongiform encephalopathy.

Feline spongiform encephalopathy (FSE), a transmissible spongiform encephalopathy or prion disease of cats, first reported in Great Britain in 1990, is believed to result from the consumption of food contaminated by the agent of bovine spongiform encephalopathy (BSE). The accumulation of PrP in non-neural tissues of cats diagnosed as suffering from FSE was investigated by immunohistochemistry. In the majority of the cats no disease-specific PrP was detected in lymphoid tissues. Small amounts of PrP were detected in the spleen of only two of 13 samples examined, in Peyer's patches of one of the two cases for which suitable material was available, but in the myenteric plexus of all four cats in which sections of intestine were examined. In addition PrP immunostaining was found in the kidney of all the cats with FSE whose kidneys were examined.

Animals↗

PubMed2001

Histological observations on the brains of symptomless 7-year-old cattle.

The histological changes in the brains of 506 clinically normal 7-year-old cattle, which were part of a cohort study on maternal transmission of bovine spongiform encephalopathy, are described. Vacuolation of the white matter, of unknown aetiology, located particularly in the substantia nigra, was a frequent finding. Vacuolated neurons were commonly observed in the red nucleus (64.3% of the animals) and in the habenular nucleus (50.1%). Spheroids were found in 10.8% of the brains, most frequently in the vestibular nuclei. Cellular inflammatory infiltrates in association with blood vessels occurred in 30% of the animals at various locations in the brain; their aetiology remains uncertain, but they may have reflected subclinical or latent infections. Mineralization of the wall of blood vessels, with proliferation of the intima, was observed frequently in vessels of the internal capsule and was probably associated with ageing. The description of histological findings in the brain of symptomless adult cattle in the present study provides a useful background for diagnostic bovine neuropathology.

Animals↗

PubMed2001

CPR-only survivors of out-of-hospital cardiac arrest: implications for out-of-hospital care and cardiac arrest research methodology.

STUDY OBJECTIVE: There is little evidence that cardiopulmonary resuscitation (CPR) alone may lead to the resuscitation of cardiac arrest victims with other than respiratory causes (eg, pediatric arrest, drowning, drug overdose). The objective of this study was to identify out-of-hospital cardiac arrest survivors resuscitated without defibrillation or advanced cardiac life support. METHODS: This observational cohort included all adult survivors of out-of-hospital cardiac arrest of a cardiac cause from phases I and II of the Ontario Prehospital Advanced Life Support Study. During the study period, the system provided a basic life support/defibrillation level of care but no advanced life support. CPR-only patients were patients determined to be without vital signs by EMS personnel who regained a palpable pulse in the field with precordial thump or CPR only and then were admitted alive to the hospital. Six members of a 7-member expert review panel had to rate the patient as either probably or definitely having an out-of-hospital cardiac arrest, and a rhythm strip consistent with a cardiac arrest rhythm had to be present to be considered a patient. Criteria considered were witness status, citizen or first responder CPR, CPR duration, arrest rhythm and rate, and performance of precordial thump. RESULTS: From January 1, 1991, to June 30, 1997, 9,667 patients with out-of-hospital cardiac arrest were treated. The overall survival rate to hospital discharge was 4.6%. There were 97 apparent CPR-only patients admitted to the hospital. Application of the inclusion criteria yielded 24 CPR-only patients who had true out-of-hospital cardiac arrest and 73 patients judged not to have cardiac arrest. Of the 24 true CPR-only patients admitted to the hospital, 15 patients were discharged alive, 10 patients were witnessed by bystanders, and 7 patients were witnessed by EMS personnel. The initial arrest rhythm was pulseless electrical activity in 9 patients, asystole in 12 patients, and ventricular tachycardia in 3 patients. One patient with ventricular tachycardia converted to sinus tachycardia with a single precordial thump. CONCLUSION: CPR-only survivors of true out-of-hospital cardiac arrest do exist; some victims of out-of-hospital cardiac arrest of primary cardiac cause can survive after provision of out-of-hospital basic life support care only. However, many patients found to be pulseless by means of out-of-hospital evaluation likely did not have a true cardiac arrest. This has implications for the survival rates of most, if not all, previous cardiac arrest reports. Survival rates from cardiac arrest may actually be lower if one excludes survivors who never had a true arrest. The absence of vital signs by out-of-hospital assessment alone is not adequate to include patients in research reports or quality evaluations for cardiac arrest.

Aged↗

PubMed2001

Canadian CT head rule study for patients with minor head injury: methodology for phase II (validation and economic analysis).

Prospective validation on a new set of patients is an essential test of a new decision rule. However, many clinical decision rules are not prospectively assessed to determine their accuracy, reliability, clinical sensibility, or potential impact on practice. This validation process is important because many statistically derived rules or guidelines do not perform well when tested in a new population. The methodologic standards for a validation study are similar to those described in the article on phase I for derivation studies in the August 2001 issue of Annals of Emergency Medicine. The goal of phase II is to prospectively assess the accuracy, reliability, and acceptability of the decision rule in a new set of patients with minor head injury. This will determine the clinical utility of the rule and is essential if such a rule is to be widely adopted into clinical practice.

Canada↗

PubMed2001

The Canadian CT Head Rule Study for patients with minor head injury: rationale, objectives, and methodology for phase I (derivation).

Head injuries are among the most common types of trauma seen in North American emergency departments, with an estimated 1 million cases seen annually. "Minor" head injury (sometimes known as "mild") is defined by a history of loss of consciousness, amnesia, or disorientation in a patient who is conscious and talking, that is, with a Glasgow Coma Scale score of 13 to 15. Although most patients with minor head injury can be discharged without sequelae after a period of observation, in a small proportion, their neurologic condition deteriorates and requires neurosurgical intervention for intracranial hematoma. The objective of the Canadian CT Head Rule Study is to develop an accurate and reliable decision rule for the use of computed tomography (CT) in patients with minor head injury. Such a decision rule would allow physicians to be more selective in their use of CT without compromising care of patients with minor head injury. This paper describes in detail the rationale, objectives, and methodology for Phase I of the study in which the decision rule was derived. [Stiell IG, Lesiuk H, Wells GA, McKnight RD, Brison R, Clement C, Eisenhauer MA, Greenberg GH, MacPhail I, Reardon M, Worthington J, Verbeek R, Rowe B, Cass D, Dreyer J, Holroyd B, Morrison L, Schull M, Laupacis A, for the Canadian CT Head and C-Spine Study Group. The Canadian CT Head Rule Study for patients with minor head injury: rationale, objectives, and methodology for phase I (derivation). Ann Emerg Med. August 2001;38:160-169.]

Adolescent↗

PubMed2001

Tolterodine versus oxybutynin in the treatment of urge urinary incontinence: a meta-analysis.

OBJECTIVE: To compare tolterodine with oxybutynin in treatment of urge incontinence. STUDY DESIGN: A systematic review, following Cochrane methods, was performed to retrieve results of randomized trials that compared tolterodine with oxybutynin in adults with urge incontinence. Composite point estimates of efficacy (episodes of incontinence per 24-hour period, frequency, and voided volume) and safety (dry mouth, withdrawal, and dose modification) were calculated. RESULTS: Four studies were included. Both drugs similarly decreased the number of micturitions in a 24-hour period. Oxybutynin was marginally superior to tolterodine in decreasing the number of incontinent episodes in a 24-hour period (weighted mean difference, 0.41; 95% confidence interval [CI], 0.04 to 0.77) and increasing the mean voided volume per micturition (8.24 mL; 95% CI, 14.19 to 3.38). Fewer patients had dry mouth (relative risk, 0.54; 95% CI, 0.48 to 0.61) and withdrew from the study because of side effects (relative risk, 0.63; 95% CI, 0.46 to 0.88) with tolterodine. CONCLUSIONS: Oxybutynin and tolterodine share a clinically similar efficacy profile (although oxybutynin is statistically superior), but tolterodine is better tolerated and leads to fewer withdrawals as a result of adverse events.

Benzhydryl Compounds↗