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Charlie H Goldsmith

Publications and source records attributed to Charlie H Goldsmith.

16 recordsLinked to original sources
PubMed2006

BLISS index for analyzing knee osteoarthritis trials data.

OBJECTIVES: Different pain thresholds were investigated, using the WOMAC Pain Scale (WOMAC-P) to determine if they could differentiate between treatment groups (hylan G-F 20 vs. appropriate care) at low and very low levels of state attainment in patients with knee osteoarthritis (OA). A method, termed the BLISS (Bellamy et al. Low Intensity Symptom State-attainment) Index, for analyzing OA knee clinical trials data, was proposed. STUDY DESIGN AND SETTING: Five analyses were performed: time to first BLISS day, BLISS days over 12 months, patients with a BLISS response at month 12, patients with a BLISS response at any time, and number of BLISS periods over 12 months. For each analysis, five levels of WOMAC-P were examined: <or=5 normalized units (NU), <or=10, <or=15, <or=20, and <or=25 (higher=more pain). RESULTS: More patients in the hylan G-F 20 group achieved BLISS states in all five analyses. These differences were statistically significant for all pain threshold levels except <or=5 NU. CONCLUSION: Five methods of measuring BLISS attainment using four prespecified threshold levels of pain were able to statistically discriminate between treatment groups. This method may potentially provide an approach, to defining which patients not only improve but also achieve a good state of health, at low and very low levels of pain intensity. BLISS-10 is a therapeutically attainable very low symptom state at which clinically important, statistically significant between-group differences are detectable, and therefore may provide a benchmark against which therapeutic interventions can be assessed. However, the value to patients, of this and other low and very low intensity pain states, requires further elaboration.

Biocompatible Materials↗
PubMed2006

Eosinophilic bronchitis in asthma: a model for establishing dose-response and relative potency of inhaled corticosteroids.

BACKGROUND: Newer generations and formulations of inhaled corticosteroids have necessitated the development of a clinically relevant model to compare their clinical potency. OBJECTIVE: We evaluated whether sputum eosinophil counts could demonstrate a dose-response to inhaled corticosteroids, and compared the response with other inflammatory markers. METHODS: Fourteen steroid-naive patients with asthma with an initial sputum eosinophilia of > or = 2.5% entered a 6-week sequential, placebo-controlled, patient-blinded, cumulative dose-response study. After 7 days of placebo, they received incremental doses of fluticasone propionate (FP), 50, 100, 200, and 400 microg/d, each for 7 days. Measurements were made of sputum and blood eosinophils, exhaled nitric oxide, spirometry, airway responsiveness to methacholine (methacholine PC20), and symptom scores before and after each dose. RESULTS: Sputum eosinophils and exhaled nitric oxide were extremely sensitive to the effects of FP, and exhibited significant dose-dependent reductions of 99.4% and 99.8 parts per billion, respectively, where each variable was expressed per 100 microg/d FP. This compared with a 0.5 doubling dose increase of airway responsiveness to methacholine and a 0.3 decrease in symptom scores. Airway responsiveness to methacholine was the only variable that increased throughout the study. CONCLUSION: These results suggest that the model of eosinophilic bronchitis could be used to compare the effect of cumulative doses of an inhaled corticosteroid delivered by different types of delivery systems or preparations using a relatively small number of patients. CLINICAL IMPLICATIONS: Future clinical studies based on this model will allow clinicians to make informed decisions regarding the relative potencies of different inhaled corticosteroids.

Administration, Inhalation↗
PubMed2006

Summary measures were a useful alternative for analyzing therapeutic clinical trial data.

BACKGROUND AND OBJECTIVE: To compare use of both a pooled index and area under the curve (AUC) to the standard analysis of a randomized controlled trial of antibiotics for patients with Alzheimer's disease. METHODS: Using data from a randomized, placebo-controlled trial of antibiotics for patients with Alzheimer's disease, a pooled index of six outcome measures was constructed. Each change score was standardized by dividing by the standard deviation, and the six standardized change scores were averaged. The Standardized Alzheimer's Disease Assessment Scale cognitive subscale and the pooled index were plotted against time and the AUC was calculated. RESULTS: The AUC analysis of the pooled index showed significant treatment effect over the 12-month period. In contrast, none of the individual measures showed an effect at more than one time point. The AUC analyses of the Standardized Alzheimer's Disease Assessment Scale cognitive subscale, the primary outcome of the trial, showed no significant difference over the entire 12-month period, although the original individual time-point analysis showed a difference at 6 months alone. CONCLUSION: Pooled indices and AUC analyses may provide important insight into therapeutic effect of agents tested in randomized clinical trials of patients with Alzheimer's disease.

Activities of Daily Living↗
PubMed2005

Evaluation of easily measured risk factors in the prediction of osteoporotic fractures.

BACKGROUND: Fracture represents the single most important clinical event in patients with osteoporosis, yet remains under-predicted. As few premonitory symptoms for fracture exist, it is of critical importance that physicians effectively and efficiently identify individuals at increased fracture risk. METHODS: Of 3426 postmenopausal women in CANDOO, 40, 158, 99, and 64 women developed a new hip, vertebral, wrist or rib fracture, respectively. Seven easily measured risk factors predictive of fracture in research trials were examined in clinical practice including: age (< 65, 65-69, 70-74, 75-79, 80+ years), rising from a chair with arms (yes, no), weight (< 57, > or = 57 kg), maternal history of hip fracture (yes, no), prior fracture after age 50 (yes, no), hip T-score (> -1, -1 to > -2.5, < or = -2.5), and current smoking status (yes, no). Multivariable logistic regression analysis was conducted. RESULTS: The inability to rise from a chair without the use of arms (3.58; 95% CI: 1.17, 10.93) was the most significant risk factor for new hip fracture. Notable risk factors for predicting new vertebral fractures were: low body weight (1.57; 95% CI: 1.04, 2.37), current smoking (1.95; 95% CI: 1.20, 3.18) and age between 75-79 years (1.96; 95% CI: 1.10, 3.51). New wrist fractures were significantly identified by low body weight (1.71, 95% CI: 1.01, 2.90) and prior fracture after 50 years (1.96; 95% CI: 1.19, 3.22). Predictors of new rib fractures include a maternal history of a hip fracture (2.89; 95% CI: 1.04, 8.08) and a prior fracture after 50 years (2.16; 95% CI: 1.20, 3.87). CONCLUSION: This study has shown that there exists a variety of predictors of future fracture, besides BMD, that can be easily assessed by a physician. The significance of each variable depends on the site of incident fracture. Of greatest interest is that an inability to rise from a chair is perhaps the most readily identifiable significant risk factor for hip fracture and can be easily incorporated into routine clinical practice.

Aged↗
PubMed2005

The effectiveness of hylan G-F 20 in patients with knee osteoarthritis: an application of two sets of response criteria developed by the OARSI and one set developed by OMERACT-OARSI.

OBJECTIVE: Secondary analyses of a previously conducted 1-year randomized controlled trial were performed to assess the application of responder criteria in patients with knee osteoarthritis (OA) using different sets of responder criteria developed by the Osteoarthritis Research Society International (OARSI) (Propositions A and B) for intra-articular drugs and Outcome Measures in Arthritis Clinical Trials (OMERACT)-OARSI (Proposition D). METHODS: Two hundred fifty-five patients with knee OA were randomized to "appropriate care with hylan G-F 20" (AC+H) or "appropriate care without hylan G-F 20" (AC). A patient was defined as a responder at month 12 based on change in Western Ontario and McMaster Universities Osteoarthritis Index pain and function (0-100 normalized scale) and patient global assessment of OA in the study knee (at least one-category improvement in very poor, poor, fair, good and very good). All propositions incorporate both minimum relative and absolute changes. RESULTS: Results demonstrated that statistically significant differences in responders between treatment groups, in favor of hylan G-F 20, were detected for Proposition A (AC+H=53.5%, AC=25.2%), Proposition B (AC+H=56.7%, AC=32.3%) and Proposition D (AC+H=66.9%, AC=42.5%). The highest effectiveness in both treatment groups was observed with Proposition D, whereas Proposition A resulted in the lowest effectiveness in both treatment groups. The treatment group differences always exceeded the required 20% minimum clinically important difference between groups established a priori, and were 28.3%, 24.4% and 24.4% for Propositions A, B and D, respectively. CONCLUSION: This analysis provides evidence for the capacity of OARSI and OMERACT-OARSI responder criteria to detect clinically important statistically detectable differences between treatment groups.

Analgesics↗
PubMed2005

Are oral bisphosphonates effective in improving lumbar bone mineral density in breast cancer survivors with osteopenia or osteoporosis?

OBJECTIVE: Breast cancer survivors with osteoporosis or osteopenia are commonly encountered in primary care and gynaecology practices. Our objective was to determine whether treatment with oral bisphosphonates (alendronate or cyclic etidronate) was more effective than calcium with vitamin D in improving lumbar spine bone mineral density (BMD) within one year in breast cancer survivors. METHODS: Breast cancer survivors with at least one year of clinical follow-up were identified from the prospective observational Canadian Database of Osteoporosis and Osteopenia (CANDOO). Analysis of covariance was used to examine the effects of bisphosphonate therapy on change in lumbar spine BMD at one year compared with the effects of calcium with vitamin D (analysis adjusted for baseline L2-L4 BMD, current tamoxifen use, number of prevalent vertebral fractures [VFs], and time since diagnosis of breast cancer, and age). RESULTS: Eighteen patients took calcium and vitamin D, 25 took cyclic etidronate, and 27 took oral alendronate. Adjusted one-year BMD increases for alendronate and cyclic etidronate compared to calcium and vitamin D were as follows: alendronate 4.53% (95% confidence interval [CI] 1.26%, 7.81%, P = 0.008), and cyclic etidronate 1.85% (-1.55%, 5.25%, P = 0.280). BMD increases were significantly greater in patients with prevalent VF compared to those without VF (P = 0.025). In contrast, time since diagnosis of breast cancer was significantly associated with a decrease in BMD (P = 0.002). We were unable to detect any effect of current tamoxifen use, baseline lumbar spine BMD, or age on changes in BMD at one year. CONCLUSION: Treatment with alendronate was associated with significantly greater improvements in lumbar spine BMD within one year in breast cancer survivors when compared with treatment with cyclic etidronate or calcium and vitamin D.

Aged↗
PubMed2004

Lack of association between vascular dementia and Chlamydia pneumoniae infection: a case-control study.

BACKGROUND: Chronic inflammation appears to play a role in the pathogenesis of vascular dementia. Given the association between Chlamydia pneumoniae and stroke, the possibility exists that previous exposure to C. pneumoniae may play a role in vascular dementia. The objective of this study was to determine if there was an association between serological evidence of C. pneumoniae infection or inflammatory markers with vascular dementia. METHODS: 28 case-patients with vascular dementia at a geriatric clinic and 24 caregiver-controls were tested for C. pneumoniae IgG and IgA antibodies. The association between vascular dementia and C. pneumoniae titres as well as inflammatory markers was estimated by using both conditional logistic regression and stratified logistic regression. RESULTS: When matched cases were compared to controls, there was no significant difference in elevated C. pneumoniae specific IgG antibodies (titre >or= 1:32), odds ratio [OR] 1.3 (95% confidence intervals [CI] 0.3 to 6.0), p = 0.71, or in elevated C. pneumoniae specific IgA antibodies (titre >or= 1:16), OR 2.0 (95%CI 0.5 to 8.0), p = 0.33 indicative of past or persistent C. pneumoniae infection. Similarly, no difference in high IgG or IgA antibody levels (IgG titre >or= 1:512 or IgA titre >or= 1:64) between the two groups, indicative of recent C. pneumoniae infection, was found, OR 0.4 (95%CI 0.1 to 2.1), p = 0.27. For C-reactive protein (CRP), the mean difference between 18 matched pairs (case - control) was - 3.33 mg/L. There was no significant difference between cases and controls when comparing log transformed values, OR 0.03 (95%CI 0.00 to 2.89), p = 0.13 or comparing CRP values above or below the median, OR 0.8 (95%CI 0.2 to 3.4), p = 0.71. For fibrinogen, the mean difference between pairs (case - control) was -0.07 g/L. There was no statistical difference between cases and controls when comparing log transformed values, OR 0.6 (95%CI 0.0 to 31.2), p = 0.79 or between fibrinogen values above and below the median, OR = 0.5 (95%CI 0.1 to 2.0), p = 0.50. CONCLUSION: We found no evidence for a significant association between C. pneumoniae infection, inflammatory markers such as CRP and fibrinogen, and vascular dementia.

Aged↗
PubMed2004

A prospective evaluation of positron emission tomography scanning, sentinel lymph node biopsy, and standard axillary dissection for axillary staging in patients with early stage breast cancer.

BACKGROUND: Positron emission tomography (PET) is a noninvasive imaging modality that can detect malignant lymph nodes. This study determined the sensitivity, specificity, predictive values, and likelihood ratios of PET scanning compared with standard axillary lymph node dissection (ALND) and sentinel lymph node biopsy (SLNB) in staging the axilla in women with early stage breast cancer. METHODS: Women with clinical stage I or II breast cancer had whole body PET scanning before ALND and SLNB, in a prospective, blinded protocol. ALND were evaluated by standard hematoxylin and eosin (H&E) staining techniques, while sentinel nodes were also examined for micrometastatic disease. RESULTS: A total of 98 patients were recruited. PET compared with ALND demonstrated sensitivity of 0.40 (95% CI, 0.16, 0.68), specificity 0.97 (CI, 0.90, 0.99), positive likelihood ratio 14.4 (CI, 3.21, 64.5), positive predictive value 0.75 (CI, 0.35, 0.97), and false-negative rate of 0.60 (CI, 0.32, 0.84). Test properties were similar for PET compared with sentinel nodes positive by H&E staining. A few false-positive scans (0.028, CI, 0.003, 0.097) were seen. Multiple logistic regression analysis found that PET accuracy was better in patients with high grade and larger tumors. Increased size and number of positive nodes were also associated with a positive PET scan. CONCLUSIONS: The sensitivity of PET compared with ALND and SLNB was low, whereas PET scanning had high specificity and positive predictive values. The study suggests that PET scanning cannot replace histologic staging in early stage breast cancer. The low rate of false-positive findings suggests that PET can identify women who can forego SLNB and require full axillary dissection.

Adult↗
PubMed2004

Muscle weakness and falls in older adults: a systematic review and meta-analysis.

OBJECTIVES: To evaluate and summarize the evidence of muscle weakness as a risk factor for falls in older adults. DESIGN: Random-effects meta-analysis. SETTING: English-language studies indexed in MEDLINE and CINAHL (1985-2002) under the key words aged and accidental falls and risk factors; bibliographies of retrieved papers. PARTICIPANTS: Fifty percent or more subjects in a study were aged 65 and older. Studies of institutionalized and community-dwelling subjects were included. MEASUREMENTS: Prospective cohort studies that included measurement of muscle strength at inception (in isolation or with other factors) with follow-up for occurrence of falls. METHODS: Sample size, population, setting, measure of muscle strength, and length of follow-up, raw data if no risk estimate, odds ratios (ORs), rate ratios, or incidence density ratios. Each study was assessed using the validity criteria: adjustment for confounders, objective definition of fall outcome, reliable method of measuring muscle strength, and blinded outcome measurement. RESULTS: Thirty studies met the selection criteria; data were available from 13. For lower extremity weakness, the combined OR was 1.76 (95% confidence interval (CI)=1.31-2.37) for any fall and 3.06 (95% CI=1.86-5.04) for recurrent falls. For upper extremity weakness the combined OR was 1.53 (95% CI=1.01-2.32) for any fall and 1.41 (95% CI=1.25-1.59) for recurrent falls. CONCLUSION: Muscle strength (especially lower extremity) should be one of the factors that is assessed and treated in older adults at risk for falls. More clinical trials are needed to isolate whether muscle-strengthening exercises are effective in preventing falls.

Accidental Falls↗
PubMed2003

Adherence to bisphosphonates and hormone replacement therapy in a tertiary care setting of patients in the CANDOO database.

Therapies for osteoporosis must be taken for at least 1 year to be effective. The purpose of this study was to determine the difference in adherence to etidronate, alendronate and hormone replacement therapy in a group of patients seen at our tertiary care centres. The Canadian Database of Osteoporosis and Osteopenia (CANDOO), a prospective observational database designed to capture clinical data, was searched for patients who started therapy following entry into CANDOO. There were 1196 initiating etidronate, 477 alendronate and 294 hormone replacement therapy women and men aged (mean, SD) 65.8 (8.7) years in the study. A Cox proportional hazards regression model was used to assess differences between treatment groups in the time to discontinuation of therapy. Several potential covariates such as anthropometry, medications, illnesses, fractures and lifestyle factors were entered into the model. A forward selection technique was used to generate the final model. Hazard ratios and 95% confidence intervals (CI) were calculated. Adjusted results indicated that alendronate-treated patients were more likely to discontinue therapy as compared with etidronate-treated patients (1.404; 95% CI: 1.150, 1.714). After 1 year, 90.3% of patients were still taking etidronate compared with 77.6% for alendronate. No statistically significant differences were found between hormone replacement therapy and etidronate users (0.971; 95% CI: 0.862, 1.093) and hormone replacement therapy and alendronate users (0.824; 95% CI: 0.624, 1.088) after controlling for potential covariates. After 1 year, 80.1% of patients were still taking hormone replacement therapy, which decreased to 44.5% after 6 years. Increasing age and presence of incident non-vertebral fractures were found to be independent predictors of adherence. In conclusion, alendronate users were more likely to discontinue therapy than etidronate users over the follow-up period. Potential barriers to long-term patient adherence to osteoporosis therapies need to be evaluated.

Aged↗
PubMed2003

Progressive resistance strengthening exercises after stroke: a single-blind randomized controlled trial.

OBJECTIVE: To determine the effectiveness of progressive resistance strengthening exercises to improve gross motor function and walking in patients receiving intensive rehabilitation after stroke. DESIGN: Randomized controlled trial. SETTING: Five inpatient rehabilitation programs affiliated with teaching hospitals. PARTICIPANTS: Inclusion criteria included less than 6 months poststroke and recovery of the leg stages 3 to 5 on the Chedoke-McMaster Stroke Assessment (CMSA). INTERVENTIONS: Both groups received conventional physical therapy programs. In addition, the experimental group performed 9 lower-extremity progressive resistance exercises 3 times a week for the duration of their stay, whereas the control group did the same exercises and for the same duration but without resistance. MAIN OUTCOME MEASURES: The Disability Inventory of the CMSA and the 2-minute walk test (2MWT) at baseline, 4 weeks, discharge, and 6 months after discharge. RESULTS: Over the length of stay, the rate of change in the Disability Inventory was.27 points per day in the experimental group and.29 points per day in the control group; the between-group difference was -.02 points per day (95% confidence interval [CI], -.10 to.06; P=.62). At discharge, the rate of change in the 2MWT was -.01 m in the experimental group and.15m in the control group; the between-group difference was -.16 m (95% CI, -.37 to.05; P=.14). CONCLUSIONS: Progressive resistance strengthening exercises as applied in our study were not effective when compared with the same exercises given without resistance.

Activities of Daily Living↗
PubMed2003

What predicts early fracture or bone loss on bisphosphonate therapy?

Factors predicting early fracture or bone loss on bisphosphonate therapy are not well defined. We studied 1588 patients over the age of 50 yr who were started on cyclic etidronate (1119) or alendronate (469) in the CANDOO (Canadian Database for Osteoporosis and Osteopenia Patients) Study. Incident fracture within 2 yr of starting therapy occurred in 31 patients and was independently predicted by a previous history of nonvertebral fracture (odds ratio [OR], 2.98, 95% confidence interval [CI], 1.30, 6.83, p = 0.010). Two hundred and fifty-seven patients lost >/=3% bone mass at the hip or spine (early bone loss) while on bisphosphonate therapy. Protection from early bone loss was most strongly independently predicted by treatment with alendronate with no previous history of etidronate use (OR, 0.29, CI, 0.13, 0.62, p = 0.002). In conclusion, early fracture on bisphosphonate therapy is most strongly predicted by a previous history of fracture and early bone loss is most strongly predicted by the potency of the prescribed bisphosphonate.

Alendronate↗
PubMed2002

The impact of incident vertebral and non-vertebral fractures on health related quality of life in postmenopausal women.

BACKGROUND: Little empirical research has examined the multiple consequences of osteoporosis on quality of life. METHODS: Health related quality of life (HRQL) was examined in relationship to incident fractures in 2009 postmenopausal women 50 years and older who were seen in consultation at our tertiary care, university teaching hospital-affiliated office and who were registered in the Canadian Database of Osteoporosis and Osteopenia (CANDOO) patients. Patients were divided into three study groups according to incident fracture status: vertebral fractures, non-vertebral fractures and no fractures. Baseline assessments of anthropometric data, medical history, therapeutic drug use, and prevalent fracture status were obtained from all participants. The disease-targeted mini-Osteoporosis Quality of Life Questionnaire (mini-OQLQ) was used to measure HRQL. RESULTS: Multiple regression analyses revealed that subjects who had experienced an incident vertebral fracture had lower HRQL difference scores as compared with non-fractured participants in total score (-0.86; 95% confidence intervals (CI): -1.30, -0.43) and the symptoms (-0.76; 95% CI: -1.23, -0.30), physical functioning (-1.12; 95% CI: -1.57, -0.67), emotional functioning (-1.06; 95% CI: -1.44, -0.68), activities of daily living (-1.47; 95% CI: -1.97, -0.96), and leisure (-0.92; 95% CI: -1.37, -0.47) domains of the mini-OQLQ. Patients who experienced an incident non-vertebral fracture had lower HRQL difference scores as compared with non-fractured participants in total score (-0.47; 95% CI: -0.70, -0.25), and the symptoms (-0.25; 95% CI: -0.49, -0.01), physical functioning (-0.39; 95% CI: -0.65, -0.14), emotional functioning (-0.97; 95% CI: -1.20, -0.75) and the activities of daily living (-0.47; 95% CI: -0.73, -0.21) domains. CONCLUSION: Quality of life decreased in patients who sustained incident vertebral and non-vertebral fractures.

Journal Article↗
PubMedDate not supplied

Clinical models to compare the safety and efficacy of inhaled corticosteroids in patients with asthma.

There is no consensus on the methods to compare the clinical efficacy of different inhaled corticosteroids. A comparison needs to be made in terms of relative potency, and studies should include two-, or preferably, three-dose comparisons. A number of clinical models and outcomes are available; they have their relative advantages and disadvantages. While measurements of symptoms and spirometry are easy and readily available, they show a flat dose-response relationship. Measurements of bronchial hyper-responsiveness to exercise and adenosine monophosphate, allergen-induced airway responses, and measurements of inflammation in sputum and exhaled air show steep dose-response relationships, particularly to low doses of inhaled steroids. An uncontrolled asthma model followed by stabilization with a short course of additional steroid, with measurements of airway responsiveness and airway inflammation, in a crossover study seems more promising than the other models. Drug deposition studies and mathematical modelling of drug pharmacokinetics in the airway may provide complementary information to clinical drug relative potency studies. Fine particle dose and emitted doses, rather than the nominal dose, should be considered in the estimation of clinical and systemic effects, respectively. When a second entry (generic) drug is being evaluated in comparison with the innovator drug (same compound and same device), it may be appropriate to consider accepting a generic as bioequivalent if it satisfies pharmaceutical equivalence.

Adrenal Cortex Hormones↗