Jinhui Ma - Academia.edu (original) (raw)
Papers by Jinhui Ma
BMC Medical Research Methodology, 2009
Background: Cluster randomized trials (CRTs) are increasingly used to assess the effectiveness of... more Background: Cluster randomized trials (CRTs) are increasingly used to assess the effectiveness of interventions to improve health outcomes or prevent diseases. However, the efficiency and consistency of using different analytical methods in the analysis of binary outcome have received little attention. We described and compared various statistical approaches in the analysis of CRTs using the Community Hypertension Assessment Trial (CHAT) as an example. The CHAT study was a cluster randomized controlled trial aimed at investigating the effectiveness of pharmacy-based blood pressure clinics led by peer health educators, with feedback to family physicians (CHAT intervention) against Usual Practice model (Control), on the monitoring and management of BP among older adults.
Neuropsychiatrie de l'Enfance et de l'Adolescence, 2012
ABSTRACT Winner of the CACAP Dalhousie Award for best paper
Archives of Osteoporosis, 2014
We determined the prospective 10-year association among incident fragility fractures and four glu... more We determined the prospective 10-year association among incident fragility fractures and four glucocorticoid (GC) treatment groups (Never GC, Prior GC, Baseline GC, and Ever GC). Results showed that GC treatment is associated with increased 10-year incident fracture risk in ambulatory men and women across Canada. Using the Canadian Multicentre Osteoporosis Study dataset, we determined the prospective 10-year association between incident fragility fractures and GC treatment. We conducted a 10-year prospective observational cohort study at nine sites across Canada. A total of 9,263 ambulatory men and women 25 years of age and older were included in the analysis. Multivariable Cox proportional hazards analyses were conducted to determine the relationship among GC treatment groups in four levels that included Never GC, Prior GC, Baseline GC, and Ever GC (combined baseline and prior groups) and time to fracture. In each of the Never GC, Prior GC, Baseline GC, and Ever GC treatment groups, the number of participants were 8,832 (95.4 %), 303 (3.3 %), 128 (1.4 %), and 431 (4.7 %), respectively. Of the 9,263 individuals enrolled, incident fragility non-spine, hip, spine, and any fractures were experienced by a total of 896 (9.67 %), 157 (1.69 %), 130 (1.40 %), and 1,102 (11.90 %) over 10-years, respectively. For men and women combined, prior GC treatment was associated with a higher hazard ratio (HR) for time to incident non-vertebral (HR = 1.5, 95 % confidence interval [CI] = 1.1, 2.0), hip (HR = 2.1, 95 % CI = 1.1, 4.0), and any fracture (HR = 1.4, 95 % CI = 1.0, 1.8) compared with never GC treatment. GC treatment is associated with increased 10-year incident fracture risk; this highlights the importance of considering therapy to prevent GC-induced fractures for patients who are using GC for various medical conditions.
Respiratory Care, 2014
BACKGROUND: Intrathoracic pressure in patients undergoing laparoscopic surgery may be affected by... more BACKGROUND: Intrathoracic pressure in patients undergoing laparoscopic surgery may be affected by intra-abdominal pressure during surgery. We investigated the relationship between intraabdominal pressure (P abd ) and esophageal pressure (P es ) in mechanically ventilated patients undergoing laparoscopic surgery. METHODS: We prospectively studied 43 consenting patients over 18 y of age who were scheduled for elective laparoscopic surgery with plans for intra-operative intubation and paralysis. After establishing a good level of inter-observer agreement on P es measurements, P es was measured by one observer for each patient using an esophageal catheter. P abd and P es were recorded before and after abdominal insufflation. We used regression analysis to model the relationship between P abd and P es . RESULTS: Patients' ages varied from 22 to 78 y, with a mean of 53.2 ؎ 14.6 y. Body mass index (BMI) varied from 13.7 to 60.5 kg/m 2 , with a mean of 33.7 ؎ 10.5. PEEP was 5-7 cm H 2 O for 19 patients and 0 cm H 2 O for the remainder. Most patients underwent gastric bypass surgery (n ؍ 11); others underwent hernia repair (n ؍ 9), colon resection (n ؍ 7), cholecystectomy (n ؍ 6), and various other surgeries (n ؍ 10). Using univariate analyses, baseline P abd was significantly correlated with baseline P es (estimate of model coefficient [95% CI]: 0.79 [0.36 -1.21], R 2 ؍ 0.24, P ؍ .001), as was BMI (0.29 [0.19 -0.40], R 2 ؍ 0.41, P < .001). However, a multivariable analysis showed no significant correlation with baseline P abd (0.10 [؊0.46 to 0.65], P ؍ .73), whereas BMI remained highly significant (0.27 [0.11-00.43], P ؍ .001) with R 2 ؍ 0.40. Due to unexpected uniformity of abdominal inflation pressures (generally 20.4 cm H 2 O) during surgery, data were not amenable to assessment of correlation between changes in abdominal and esophageal pressures after inflation. CONCLUSION: There was a limited correlation between baseline P es and P abd in patients undergoing elective laparoscopic surgery, suggesting a limited value of P abd measurements in the management of mechanically ventilated patients.
Journal of clinical densitometry : the official journal of the International Society for Clinical Densitometry, 2015
A number of unusual conditions cause decreased bone mass and density in children and these may be... more A number of unusual conditions cause decreased bone mass and density in children and these may be associated with low-trauma fractures. However, a series of reports have more recently identified that children with chronic disease sustain vertebral fractures (VFs) much more often than had been suspected. The common denominator involved is glucocorticoid (GC) administration, although other factors such as disease activity come into play. This review will focus on the imaging findings in this form of secondary osteoporosis. Spinal fractures in children have been found to correlate with back pain. At the same time, up to 2/3 of children with VFs in the GC-treated setting are asymptomatic, underscoring the importance of routine surveillance in at-risk children. Other predictors of prevalent and incident VFs include GC exposure (average daily and cumulative dose), declines in lumbar spine bone mineral density Z-scores and increases in body mass index Z-scores, as well as increases in dise...
ABSTRACT Objectives:(1) Compare effectiveness and adverse events of interventions (pharmacologica... more ABSTRACT Objectives:(1) Compare effectiveness and adverse events of interventions (pharmacological, psychosocial, or behavioral, and the combination of pharmacological and psychosocial or behavioral interventions) for preschoolers at high risk for attention deficit hyperactivity disorder (ADHD); (2) compare long-term effectiveness and adverse events of interventions for ADHD among persons of all ages; and (3) describe how identification and treatment for ADHD vary by geography, time period, provider type, and sociodemographic characteristics, compared with endemic prevalence. Data Sources:MEDLINE®, Cochrane CENTRAL, EMBASE, PsycInfo, and ERIC (Education Resources Information Center) were searched from 1980 to May 31, 2010. Reference lists of included studies and gray literature were searched manually. Review Methods:Reviewers applied preset criteria to screen all citations. Decisions required agreement between two independent reviewers, with disagreements regarding inclusion or exclusion resolved by a third. The Effective Public Health Practice Project (EPHPP) process was used to evaluate internal validity of publications regarding interventions for preschoolers at high risk of ADHD and long-term outcomes following interventions for ADHD in persons of all ages. Overall strength of the evidence (SOE) was assessed using the GRADE approach, accounting for risk of bias and study design, consistency of results, directness of evidence, and degree of certainty regarding outcomes of interest. Results:Of included studies, only a subset could be pooled statistically using meta-analytic techniques. For the first objective, we rated as “good” quality eight studies of parent behavior training (PBT) with 424 participants. These demonstrated high SOE for improving child behavior (standardized mean difference [SMD] = −0.68; 95-percent confidence interval [CI], −0.88 to −0.47). A single “good” quality study of methylphenidate (MPH) with 114 preschool children provided low SOE for improving child behavior (SMD = −0.83; 95-percent CI, −1.21 to −0.44). Adverse effects were present for preschool children treated with MPH; adverse effects were not mentioned for PBT. For the second objective, the majority of studies were open extension trials without continuation of untreated comparison groups. Evidence from the single “good” quality study of MPH demonstrated low SOE for reduction of symptoms, with SMD = −0.54 (95-percent CI, −0.79 to −0.29). Evidence from the single “good” quality study of atomoxetine demonstrated low SOE for reduction of symptoms, with SMD = −0.40 (95-percent CI, −0.61 to −0.18). Evidence from the single “good” quality study of combined psychostimulant medication with behavioral/psychosocial interventions provided low SOE, with SMD = −0.70 (95-percent CI, −0.95 to −0.46). Safety reports for pharmacological interventions derived from observational studies on uncontrolled extensions of clinical trials, as well as from administrative databases, provided inconclusive evidence for growth, cerebrovascular, and cardiac adverse effects. Evidence that psychostimulant use in childhood improves long-term outcomes was inconclusive. For the third objective, a discussion of contextual issues and factors relating to underlying prevalence and rates of diagnosis and treatment was included. Population-based data were relatively scarce and lacked uniform methods and settings, which interfered with interpretation. The available evidence suggested that underlying prevalence of ADHD varies less than rates of diagnosis and treatment. Patterns of diagnosis and treatment appeared to be associated with such factors as locale, time period, and patient or provider characteristics. Conclusions:The SOE for PBT as the first-line intervention for improved behavior among preschoolers at risk for ADHD was high, while the SOE for methylphenidate for improved behavior among preschoolers was low. Evidence regarding long-term outcomes following interventions for ADHD was sparse among persons of all ages, and therefore inconclusive, with one exception. Primary school–age children, mostly boys with ADHD combined type, showed improvements in symptomatic behavior maintained for 12 to 14 months using pharmacological agents, specifically methylphenidate medication management or atomoxetine. Other subgroups, interventions, and long-term outcomes were under-researched. Evidence regarding large-scale patterns of diagnosis and treatment compared with endemic rates of disorder was inconclusive.
Canadian Respiratory Journal Journal of the Canadian Thoracic Society, Mar 28, 2014
Studies comparing continuous renal replacement therapy modalities are lacking. Theoretically, con... more Studies comparing continuous renal replacement therapy modalities are lacking. Theoretically, continuous venovenous hemofiltration (CVVH) could be more effective than continuous venovenous hemodiafiltration (CVVHDF), and may be associated with fewer complications; however, there are no published data to support this hypothesis. To examine the effect of CVVH on mortality and other clinically important outcomes compared with CVVHDF in the intensive care unit (ICU) setting. Using a log of all continuous renal replacement therapy performed at a Canadian tertiary centre between 2007 and 2010, the records of patients meeting the inclusion criteria of being admitted to the ICU, and receiving either CVVH or CVVHDF for management of acute renal failure, were reviewed. The information retrieved included demographic data, death events, and hospital and ICU length of stay. Data from 153 patients were included in the present study. Hospital and 30-day mortality were similar in the CVVH and CVVHDF groups (OR 0.85 [95% CI 0.38 to 1.89]; P=0.69 and OR 1.35 [95% CI 0.62 to 2.95]; P=0.45, respectively). There was no difference in hospital length of stay (mean difference -34.14 [95% CI -72.92 to 4.65]; P=0.08). The present retrospective review suggests that the use of CVVH does not reduce mortality or hospital length of stay when compared with CVVHDF. Future randomized trials should control for different patient populations and continue to evaluate the removal of small molecules such as hormones.
The Journal of Clinical Endocrinology & Metabolism, 2015
To determine the incidence and predictors of vertebral fractures (VF) during the four years follo... more To determine the incidence and predictors of vertebral fractures (VF) during the four years following diagnosis in pediatric acute lymphoblastic leukemia (ALL). Children were enrolled within 30 days of chemotherapy initiation, with incident VF assessed annually on lateral spine radiographs according to the Genant method. Extended Cox&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s models assessed the association between incident VF and clinical predictors. 186 children with ALL completed the baseline evaluation (median age 5.3 years, interquartile range 3.4 to 9.7, 58% boys). The VF incidence rate was 8.7 per 100 person-years, with a four-year cumulative incidence of 26.4%. The highest annual incidence occurred at 12 months (16.1%; 95% confidence interval (CI) 11.2, 22.7), falling to 2.9% at four years (95% CI 1.1, 7.3). Half of the children with incident VF had moderate or severe VF and 39% of those with incident VF were asymptomatic. Every 10 mg/m(2) increase in average daily glucocorticoid dose (prednisone equivalents) was associated with a 5.9-fold increased VF risk (95% CI 3.0, 11.8; p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01). Other predictors of increased VF risk included: VF at diagnosis, younger age, and lower spine bone mineral density Z-scores at baseline and each annual assessment. One quarter of children with ALL developed incident VF in the four years following diagnosis; most of the VF burden was in the first year. Over one third of children with incident VF were asymptomatic. Discrete clinical predictors of VF were evident early in the patient&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s clinical course, including VF at diagnosis. Incident vertebral fractures (VF) occur in 26% of children with acute lymphoblastic leukemia in the four years following diagnosis, with the highest risk at 12 months. VF at diagnosis, whether symptomatic or not, are the strongest predictors of incident VF over four years.
Canadian respiratory journal : journal of the Canadian Thoracic Society
Studies comparing continuous renal replacement therapy modalities are lacking. Theoretically, con... more Studies comparing continuous renal replacement therapy modalities are lacking. Theoretically, continuous venovenous hemofiltration (CVVH) could be more effective than continuous venovenous hemodiafiltration (CVVHDF), and may be associated with fewer complications; however, there are no published data to support this hypothesis. To examine the effect of CVVH on mortality and other clinically important outcomes compared with CVVHDF in the intensive care unit (ICU) setting. Using a log of all continuous renal replacement therapy performed at a Canadian tertiary centre between 2007 and 2010, the records of patients meeting the inclusion criteria of being admitted to the ICU, and receiving either CVVH or CVVHDF for management of acute renal failure, were reviewed. The information retrieved included demographic data, death events, and hospital and ICU length of stay. Data from 153 patients were included in the present study. Hospital and 30-day mortality were similar in the CVVH and CVVHD...
BMC musculoskeletal disorders, 2014
Individuals with diabetes have been found previously to be at increased risk of non-traumatic fra... more Individuals with diabetes have been found previously to be at increased risk of non-traumatic fracture. However, it is unclear if these individuals are being identified and treated for osteoporosis. 7753 Canadians over 50 years of age were followed prospectively for 10 years. 606/7753 (7.8%) of had diabetes; 98 were insulin-dependent and 508 were not. Using a cox proportional hazards model, we assessed the association between diabetes status and incident non-traumatic fracture. Using logistic regression we identified factors associated with bisphosphonate use over the 10 year period of study. Mean (SD) age of participants was 66.7(9.4) years and 72% were female. Those with diabetes had higher BMD T-scores at baseline, with a mean (SD) femoral neck T-Score of -0.97 (1.06), compared to -1.24 (0.99) in the general cohort. The adjusted hazard ratio (HR) for incident non-traumatic fracture in individuals with insulin-dependent diabetes over the 10 year study period was 2.50 (95% confiden...
Journal of Bone and Mineral Research, 2015
Vertebral fractures are an important yet under-recognized manifestation of osteoporosis in childr... more Vertebral fractures are an important yet under-recognized manifestation of osteoporosis in children with chronic, glucocorticoid-treated illnesses. Our goal was to determine the incidence and clinical predictors of vertebral fractures in the three years following glucocorticoid initiation among pediatric patients with rheumatic disorders. Incident vertebral fractures were evaluated according to the Genant semi-quantitative method on lateral radiographs at baseline and then annually in the 3 years following glucocorticoid initiation. Extended Cox models were used to assess the association between vertebral fractures and clinical risk predictors. 134 children with rheumatic disorders were enrolled in the study (mean ± standard deviation (SD) age 9.9±4.4 years, 65% girls). The unadjusted vertebral fracture incidence rate was 4.4 per 100 person-years, with a three-year incidence proportion of 12.4%. The highest annual incidence occurred in the first year (6.0%, 95% confidence interval (CI) 2.9-11.7). Almost half of the patients with fractures were asymptomatic. Every 0.5 mg/kg increase in average daily glucocorticoid (prednisone equivalents) dose was associated with a 2.0-fold increased fracture risk (hazard ratio (HR) 2.0, 95% CI 1.1-3.5). Other predictors of increased vertebral fracture risk included: (1) Increases in disease severity scores between baseline and 12 months, (2) Increases in body mass index Z-scores in the first 6 of each 12-month period preceding the annual fracture assessment, and (3) Decreases in lumbar spine bone mineral density Z-scores in the first 6 months of glucocorticoid therapy. As such, we observed that a clinically significant number of children with rheumatic disorders developed incident vertebral fractures in the three years following glucocorticoid initiation. Almost half of the children were asymptomatic and thereby would have been undiagnosed in the absence of radiographic monitoring. In addition, discrete clinical predictors of incident vertebral fractures were evident early in the course of glucocorticoid therapy. This article is protected by copyright. All rights reserved.
ISRN Epidemiology, 2013
Objective. Individuals with diabetes have been found to be at increased risk of nontraumatic frac... more Objective. Individuals with diabetes have been found to be at increased risk of nontraumatic fracture. However, within the diabetic population, how to distinguish who is at the highest risk and warranting therapy has remained elusive. Design. Cross-sectional analysis of a national population-based cohort study. Patients. Men and women over the age of 50 with diabetes from across Canada. Measurements. Logistic regression analysis to identify diabetes specific factors associated with a history of one or more nontraumatic fractures. Results. Six hundred and six individuals with diabetes with a mean age of 69 years were examined. Thirty percent had a history of non-traumatic fracture. Macrovascular diseases in the form of stroke or TIA, as well as hypertension, were found to be independently associated with fragility fracture. Other, more traditional, clinical risk factors were also associated with fracture, including increased age, female gender, rheumatoid arthritis, family history of osteoporosis, and decreased bone mineral density. Conclusions. In this cohort of Canadians with diabetes, those with rheumatoid arthritis, a family history of osteoporosis, female gender, increased age, decreased BMD, cerebrovascular disease, or hypertension were more likely to have had a non-traumatic fracture. These risk factors may be important to clinicians when identifying which of their diabetic patients are at highest risk of fracture and in need of preventative therapies.
Open Access Medical Statistics, 2012
Introduction: Although researchers have proposed various strategies to handle missing outcomes in... more Introduction: Although researchers have proposed various strategies to handle missing outcomes in cluster randomized trials (CRTs), limited attention has been paid to the performance of these strategies. Under the assumption of covariate-dependent missingness, the objective of this simulation study is to compare the performance of various strategies in handling missing binary outcomes in CRTs under different design settings. Methods: There are six missing data strategies investigated in this paper, which include complete case analysis, standard multiple imputation (MI) strategies using either logistic regression or Markov chain Monte Carlo (MCMC) method, within-cluster MI strategies using either logistic regression or MCMC method, and MI using logistic regression with cluster as a fixed effect. The performance of these strategies is evaluated through bias, empirical standard error, root mean squared error, and coverage probability. Results: Under the assumption of covariate-dependent missingness and applying the generalized estimating equations approach for fitting the logistic regression, it was shown that complete case analysis yields valid inferences when the percentage of missing outcomes is not large (,20%) for all the designs of CRTs considered in this paper. Standard MI strategies can be adopted when the design effect is small (variance inflation factor [VIF] # 3); however, they tend to underestimate the standard error of treatment effect when the design effect is large. Within-cluster MI strategy using logistic regression is valid for imputation of missing data from CRTs, especially when the cluster size is large (.50) and the design effect is large (VIF . 3). In contrast, within-cluster MI strategy using MCMC method may yield biased estimates of treatment effect for CRTs with small cluster size (#50). MI using logistic regression with cluster as a fixed effect may substantially overestimate the standard error of the estimated treatment effect when the intracluster correlation coefficient is small. It may also lead to biased estimated treatment effect. Conclusion: Findings from this simulation study provide researchers with quantitative evidence to guide selection of an appropriate strategy to deal with missing binary outcomes.
The Journal of Clinical Endocrinology & Metabolism, 2014
Our objectives were to assess the magnitude of the disparity in lumbar spine bone mineral density... more Our objectives were to assess the magnitude of the disparity in lumbar spine bone mineral density (LSBMD) Z-scores generated by different reference databases and to evaluate whether the relationship between LSBMD Z-scores and vertebral fractures (VF) varies by choice of database. Children with leukemia underwent LSBMD by cross-calibrated dual-energy x-ray absorptiometry, with Z-scores generated according to Hologic and Lunar databases. VF were assessed by the Genant method on spine radiographs. Logistic regression was used to assess the association between fractures and LSBMD Z-scores. Net reclassification improvement and area under the receiver operating characteristic curve were calculated to assess the predictive accuracy of LSBMD Z-scores for VF. For the 186 children from 0 to 18 years of age, 6 different age ranges were studied. The Z-scores generated for the 0 to 18 group were highly correlated (r ≥ 0.90), but the proportion of children with LSBMD Z-scores ≤-2.0 among those with VF varied substantially (from 38-66%). Odds ratios (OR) for the association between LSBMD Z-score and VF were similar regardless of database (OR = 1.92, 95% confidence interval 1.44, 2.56 to OR = 2.70, 95% confidence interval 1.70, 4.28). Area under the receiver operating characteristic curve and net reclassification improvement ranged from 0.71 to 0.75 and -0.15 to 0.07, respectively. Although the use of a LSBMD Z-score threshold as part of the definition of osteoporosis in a child with VF does not appear valid, the study of relationships between BMD and VF is valid regardless of the BMD database that is used.
Canadian Journal of Anesthesia/Journal canadien d'anesthésie, 2013
Purpose The primary objectives of this historical casecontrol study were to evaluate the incidenc... more Purpose The primary objectives of this historical casecontrol study were to evaluate the incidence of and reasons and risk factors for adult unanticipated admissions in three tertiary care Canadian hospitals following ambulatory surgery. Methods A random sample of 200 patients requiring admission (cases) and 200 patients not requiring admission (controls) was taken from 20,657 ambulatory procedures was identified and compared. The following variables were included: demographics, reason for admission, type of anesthesia, surgical procedure, length of procedure, American Society of Anesthesiologists' (ASA) classification, surgical completion time, pre-anesthesia clinic, medical history, medications (classes), and perioperative complications. Multiple logistic regression analysis was used to assess factors associated with unanticipated admissions.
BMC Medical Research Methodology, 2009
Background: Cluster randomized trials (CRTs) are increasingly used to assess the effectiveness of... more Background: Cluster randomized trials (CRTs) are increasingly used to assess the effectiveness of interventions to improve health outcomes or prevent diseases. However, the efficiency and consistency of using different analytical methods in the analysis of binary outcome have received little attention. We described and compared various statistical approaches in the analysis of CRTs using the Community Hypertension Assessment Trial (CHAT) as an example. The CHAT study was a cluster randomized controlled trial aimed at investigating the effectiveness of pharmacy-based blood pressure clinics led by peer health educators, with feedback to family physicians (CHAT intervention) against Usual Practice model (Control), on the monitoring and management of BP among older adults.
BMC Medical Research Methodology, 2011
Background: Attrition, which leads to missing data, is a common problem in cluster randomized tri... more Background: Attrition, which leads to missing data, is a common problem in cluster randomized trials (CRTs), where groups of patients rather than individuals are randomized. Standard multiple imputation (MI) strategies may not be appropriate to impute missing data from CRTs since they assume independent data. In this paper, under the assumption of missing completely at random and covariate dependent missing, we compared six MI strategies which account for the intra-cluster correlation for missing binary outcomes in CRTs with the standard imputation strategies and complete case analysis approach using a simulation study. Method: We considered three within-cluster and three across-cluster MI strategies for missing binary outcomes in CRTs. The three within-cluster MI strategies are logistic regression method, propensity score method, and Markov chain Monte Carlo (MCMC) method, which apply standard MI strategies within each cluster. The three acrosscluster MI strategies are propensity score method, random-effects (RE) logistic regression approach, and logistic regression with cluster as a fixed effect. Based on the community hypertension assessment trial (CHAT) which has complete data, we designed a simulation study to investigate the performance of above MI strategies. Results: The estimated treatment effect and its 95% confidence interval (CI) from generalized estimating equations (GEE) model based on the CHAT complete dataset are 1.14 (0.76 1.70). When 30% of binary outcome are missing completely at random, a simulation study shows that the estimated treatment effects and the corresponding 95% CIs from GEE model are 1.15 (0.76 1.75) if complete case analysis is used, 1.12 (0.72 1.73) if within-cluster MCMC method is used, 1.21 (0.80 1.81) if across-cluster RE logistic regression is used, and 1.16 (0.82 1.64) if standard logistic regression which does not account for clustering is used. Conclusion: When the percentage of missing data is low or intra-cluster correlation coefficient is small, different approaches for handling missing binary outcome data generate quite similar results. When the percentage of missing data is large, standard MI strategies, which do not take into account the intra-cluster correlation, underestimate the variance of the treatment effect. Within-cluster and across-cluster MI strategies (except for random-effects logistic regression MI strategy), which take the intra-cluster correlation into account, seem to be more appropriate to handle the missing outcome from CRTs. Under the same imputation strategy and percentage of missingness, the estimates of the treatment effect from GEE and RE logistic regression models are similar.
BMC Medical Research Methodology, 2011
Background: Multicentre randomized controlled trials (RCTs) routinely use randomization and analy... more Background: Multicentre randomized controlled trials (RCTs) routinely use randomization and analysis stratified by centre to control for differences between centres and to improve precision. No consensus has been reached on how to best analyze correlated continuous outcomes in such settings. Our objective was to investigate the properties of commonly used statistical models at various levels of clustering in the context of multicentre RCTs. Methods: Assuming no treatment by centre interaction, we compared six methods (ignoring centre effects, including centres as fixed effects, including centres as random effects, generalized estimating equation (GEE), and fixed-and random-effects centre-level analysis) to analyze continuous outcomes in multicentre RCTs using simulations over a wide spectrum of intraclass correlation (ICC) values, and varying numbers of centres and centre size. The performance of models was evaluated in terms of bias, precision, mean squared error of the point estimator of treatment effect, empirical coverage of the 95% confidence interval, and statistical power of the procedure. Results: While all methods yielded unbiased estimates of treatment effect, ignoring centres led to inflation of standard error and loss of statistical power when within centre correlation was present. Mixed-effects model was most efficient and attained nominal coverage of 95% and 90% power in almost all scenarios. Fixed-effects model was less precise when the number of centres was large and treatment allocation was subject to chance imbalance within centre. GEE approach underestimated standard error of the treatment effect when the number of centres was small. The two centre-level models led to more variable point estimates and relatively low interval coverage or statistical power depending on whether or not heterogeneity of treatment contrasts was considered in the analysis.
BMC Medical Research Methodology, 2013
Background: The objective of this simulation study is to compare the accuracy and efficiency of p... more Background: The objective of this simulation study is to compare the accuracy and efficiency of population-averaged (i.e. generalized estimating equations (GEE)) and cluster-specific (i.e. random-effects logistic regression (RELR)) models for analyzing data from cluster randomized trials (CRTs) with missing binary responses.
BMC Medical Research Methodology, 2009
Background: Cluster randomized trials (CRTs) are increasingly used to assess the effectiveness of... more Background: Cluster randomized trials (CRTs) are increasingly used to assess the effectiveness of interventions to improve health outcomes or prevent diseases. However, the efficiency and consistency of using different analytical methods in the analysis of binary outcome have received little attention. We described and compared various statistical approaches in the analysis of CRTs using the Community Hypertension Assessment Trial (CHAT) as an example. The CHAT study was a cluster randomized controlled trial aimed at investigating the effectiveness of pharmacy-based blood pressure clinics led by peer health educators, with feedback to family physicians (CHAT intervention) against Usual Practice model (Control), on the monitoring and management of BP among older adults.
Neuropsychiatrie de l'Enfance et de l'Adolescence, 2012
ABSTRACT Winner of the CACAP Dalhousie Award for best paper
Archives of Osteoporosis, 2014
We determined the prospective 10-year association among incident fragility fractures and four glu... more We determined the prospective 10-year association among incident fragility fractures and four glucocorticoid (GC) treatment groups (Never GC, Prior GC, Baseline GC, and Ever GC). Results showed that GC treatment is associated with increased 10-year incident fracture risk in ambulatory men and women across Canada. Using the Canadian Multicentre Osteoporosis Study dataset, we determined the prospective 10-year association between incident fragility fractures and GC treatment. We conducted a 10-year prospective observational cohort study at nine sites across Canada. A total of 9,263 ambulatory men and women 25 years of age and older were included in the analysis. Multivariable Cox proportional hazards analyses were conducted to determine the relationship among GC treatment groups in four levels that included Never GC, Prior GC, Baseline GC, and Ever GC (combined baseline and prior groups) and time to fracture. In each of the Never GC, Prior GC, Baseline GC, and Ever GC treatment groups, the number of participants were 8,832 (95.4 %), 303 (3.3 %), 128 (1.4 %), and 431 (4.7 %), respectively. Of the 9,263 individuals enrolled, incident fragility non-spine, hip, spine, and any fractures were experienced by a total of 896 (9.67 %), 157 (1.69 %), 130 (1.40 %), and 1,102 (11.90 %) over 10-years, respectively. For men and women combined, prior GC treatment was associated with a higher hazard ratio (HR) for time to incident non-vertebral (HR = 1.5, 95 % confidence interval [CI] = 1.1, 2.0), hip (HR = 2.1, 95 % CI = 1.1, 4.0), and any fracture (HR = 1.4, 95 % CI = 1.0, 1.8) compared with never GC treatment. GC treatment is associated with increased 10-year incident fracture risk; this highlights the importance of considering therapy to prevent GC-induced fractures for patients who are using GC for various medical conditions.
Respiratory Care, 2014
BACKGROUND: Intrathoracic pressure in patients undergoing laparoscopic surgery may be affected by... more BACKGROUND: Intrathoracic pressure in patients undergoing laparoscopic surgery may be affected by intra-abdominal pressure during surgery. We investigated the relationship between intraabdominal pressure (P abd ) and esophageal pressure (P es ) in mechanically ventilated patients undergoing laparoscopic surgery. METHODS: We prospectively studied 43 consenting patients over 18 y of age who were scheduled for elective laparoscopic surgery with plans for intra-operative intubation and paralysis. After establishing a good level of inter-observer agreement on P es measurements, P es was measured by one observer for each patient using an esophageal catheter. P abd and P es were recorded before and after abdominal insufflation. We used regression analysis to model the relationship between P abd and P es . RESULTS: Patients' ages varied from 22 to 78 y, with a mean of 53.2 ؎ 14.6 y. Body mass index (BMI) varied from 13.7 to 60.5 kg/m 2 , with a mean of 33.7 ؎ 10.5. PEEP was 5-7 cm H 2 O for 19 patients and 0 cm H 2 O for the remainder. Most patients underwent gastric bypass surgery (n ؍ 11); others underwent hernia repair (n ؍ 9), colon resection (n ؍ 7), cholecystectomy (n ؍ 6), and various other surgeries (n ؍ 10). Using univariate analyses, baseline P abd was significantly correlated with baseline P es (estimate of model coefficient [95% CI]: 0.79 [0.36 -1.21], R 2 ؍ 0.24, P ؍ .001), as was BMI (0.29 [0.19 -0.40], R 2 ؍ 0.41, P < .001). However, a multivariable analysis showed no significant correlation with baseline P abd (0.10 [؊0.46 to 0.65], P ؍ .73), whereas BMI remained highly significant (0.27 [0.11-00.43], P ؍ .001) with R 2 ؍ 0.40. Due to unexpected uniformity of abdominal inflation pressures (generally 20.4 cm H 2 O) during surgery, data were not amenable to assessment of correlation between changes in abdominal and esophageal pressures after inflation. CONCLUSION: There was a limited correlation between baseline P es and P abd in patients undergoing elective laparoscopic surgery, suggesting a limited value of P abd measurements in the management of mechanically ventilated patients.
Journal of clinical densitometry : the official journal of the International Society for Clinical Densitometry, 2015
A number of unusual conditions cause decreased bone mass and density in children and these may be... more A number of unusual conditions cause decreased bone mass and density in children and these may be associated with low-trauma fractures. However, a series of reports have more recently identified that children with chronic disease sustain vertebral fractures (VFs) much more often than had been suspected. The common denominator involved is glucocorticoid (GC) administration, although other factors such as disease activity come into play. This review will focus on the imaging findings in this form of secondary osteoporosis. Spinal fractures in children have been found to correlate with back pain. At the same time, up to 2/3 of children with VFs in the GC-treated setting are asymptomatic, underscoring the importance of routine surveillance in at-risk children. Other predictors of prevalent and incident VFs include GC exposure (average daily and cumulative dose), declines in lumbar spine bone mineral density Z-scores and increases in body mass index Z-scores, as well as increases in dise...
ABSTRACT Objectives:(1) Compare effectiveness and adverse events of interventions (pharmacologica... more ABSTRACT Objectives:(1) Compare effectiveness and adverse events of interventions (pharmacological, psychosocial, or behavioral, and the combination of pharmacological and psychosocial or behavioral interventions) for preschoolers at high risk for attention deficit hyperactivity disorder (ADHD); (2) compare long-term effectiveness and adverse events of interventions for ADHD among persons of all ages; and (3) describe how identification and treatment for ADHD vary by geography, time period, provider type, and sociodemographic characteristics, compared with endemic prevalence. Data Sources:MEDLINE®, Cochrane CENTRAL, EMBASE, PsycInfo, and ERIC (Education Resources Information Center) were searched from 1980 to May 31, 2010. Reference lists of included studies and gray literature were searched manually. Review Methods:Reviewers applied preset criteria to screen all citations. Decisions required agreement between two independent reviewers, with disagreements regarding inclusion or exclusion resolved by a third. The Effective Public Health Practice Project (EPHPP) process was used to evaluate internal validity of publications regarding interventions for preschoolers at high risk of ADHD and long-term outcomes following interventions for ADHD in persons of all ages. Overall strength of the evidence (SOE) was assessed using the GRADE approach, accounting for risk of bias and study design, consistency of results, directness of evidence, and degree of certainty regarding outcomes of interest. Results:Of included studies, only a subset could be pooled statistically using meta-analytic techniques. For the first objective, we rated as “good” quality eight studies of parent behavior training (PBT) with 424 participants. These demonstrated high SOE for improving child behavior (standardized mean difference [SMD] = −0.68; 95-percent confidence interval [CI], −0.88 to −0.47). A single “good” quality study of methylphenidate (MPH) with 114 preschool children provided low SOE for improving child behavior (SMD = −0.83; 95-percent CI, −1.21 to −0.44). Adverse effects were present for preschool children treated with MPH; adverse effects were not mentioned for PBT. For the second objective, the majority of studies were open extension trials without continuation of untreated comparison groups. Evidence from the single “good” quality study of MPH demonstrated low SOE for reduction of symptoms, with SMD = −0.54 (95-percent CI, −0.79 to −0.29). Evidence from the single “good” quality study of atomoxetine demonstrated low SOE for reduction of symptoms, with SMD = −0.40 (95-percent CI, −0.61 to −0.18). Evidence from the single “good” quality study of combined psychostimulant medication with behavioral/psychosocial interventions provided low SOE, with SMD = −0.70 (95-percent CI, −0.95 to −0.46). Safety reports for pharmacological interventions derived from observational studies on uncontrolled extensions of clinical trials, as well as from administrative databases, provided inconclusive evidence for growth, cerebrovascular, and cardiac adverse effects. Evidence that psychostimulant use in childhood improves long-term outcomes was inconclusive. For the third objective, a discussion of contextual issues and factors relating to underlying prevalence and rates of diagnosis and treatment was included. Population-based data were relatively scarce and lacked uniform methods and settings, which interfered with interpretation. The available evidence suggested that underlying prevalence of ADHD varies less than rates of diagnosis and treatment. Patterns of diagnosis and treatment appeared to be associated with such factors as locale, time period, and patient or provider characteristics. Conclusions:The SOE for PBT as the first-line intervention for improved behavior among preschoolers at risk for ADHD was high, while the SOE for methylphenidate for improved behavior among preschoolers was low. Evidence regarding long-term outcomes following interventions for ADHD was sparse among persons of all ages, and therefore inconclusive, with one exception. Primary school–age children, mostly boys with ADHD combined type, showed improvements in symptomatic behavior maintained for 12 to 14 months using pharmacological agents, specifically methylphenidate medication management or atomoxetine. Other subgroups, interventions, and long-term outcomes were under-researched. Evidence regarding large-scale patterns of diagnosis and treatment compared with endemic rates of disorder was inconclusive.
Canadian Respiratory Journal Journal of the Canadian Thoracic Society, Mar 28, 2014
Studies comparing continuous renal replacement therapy modalities are lacking. Theoretically, con... more Studies comparing continuous renal replacement therapy modalities are lacking. Theoretically, continuous venovenous hemofiltration (CVVH) could be more effective than continuous venovenous hemodiafiltration (CVVHDF), and may be associated with fewer complications; however, there are no published data to support this hypothesis. To examine the effect of CVVH on mortality and other clinically important outcomes compared with CVVHDF in the intensive care unit (ICU) setting. Using a log of all continuous renal replacement therapy performed at a Canadian tertiary centre between 2007 and 2010, the records of patients meeting the inclusion criteria of being admitted to the ICU, and receiving either CVVH or CVVHDF for management of acute renal failure, were reviewed. The information retrieved included demographic data, death events, and hospital and ICU length of stay. Data from 153 patients were included in the present study. Hospital and 30-day mortality were similar in the CVVH and CVVHDF groups (OR 0.85 [95% CI 0.38 to 1.89]; P=0.69 and OR 1.35 [95% CI 0.62 to 2.95]; P=0.45, respectively). There was no difference in hospital length of stay (mean difference -34.14 [95% CI -72.92 to 4.65]; P=0.08). The present retrospective review suggests that the use of CVVH does not reduce mortality or hospital length of stay when compared with CVVHDF. Future randomized trials should control for different patient populations and continue to evaluate the removal of small molecules such as hormones.
The Journal of Clinical Endocrinology & Metabolism, 2015
To determine the incidence and predictors of vertebral fractures (VF) during the four years follo... more To determine the incidence and predictors of vertebral fractures (VF) during the four years following diagnosis in pediatric acute lymphoblastic leukemia (ALL). Children were enrolled within 30 days of chemotherapy initiation, with incident VF assessed annually on lateral spine radiographs according to the Genant method. Extended Cox&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s models assessed the association between incident VF and clinical predictors. 186 children with ALL completed the baseline evaluation (median age 5.3 years, interquartile range 3.4 to 9.7, 58% boys). The VF incidence rate was 8.7 per 100 person-years, with a four-year cumulative incidence of 26.4%. The highest annual incidence occurred at 12 months (16.1%; 95% confidence interval (CI) 11.2, 22.7), falling to 2.9% at four years (95% CI 1.1, 7.3). Half of the children with incident VF had moderate or severe VF and 39% of those with incident VF were asymptomatic. Every 10 mg/m(2) increase in average daily glucocorticoid dose (prednisone equivalents) was associated with a 5.9-fold increased VF risk (95% CI 3.0, 11.8; p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01). Other predictors of increased VF risk included: VF at diagnosis, younger age, and lower spine bone mineral density Z-scores at baseline and each annual assessment. One quarter of children with ALL developed incident VF in the four years following diagnosis; most of the VF burden was in the first year. Over one third of children with incident VF were asymptomatic. Discrete clinical predictors of VF were evident early in the patient&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s clinical course, including VF at diagnosis. Incident vertebral fractures (VF) occur in 26% of children with acute lymphoblastic leukemia in the four years following diagnosis, with the highest risk at 12 months. VF at diagnosis, whether symptomatic or not, are the strongest predictors of incident VF over four years.
Canadian respiratory journal : journal of the Canadian Thoracic Society
Studies comparing continuous renal replacement therapy modalities are lacking. Theoretically, con... more Studies comparing continuous renal replacement therapy modalities are lacking. Theoretically, continuous venovenous hemofiltration (CVVH) could be more effective than continuous venovenous hemodiafiltration (CVVHDF), and may be associated with fewer complications; however, there are no published data to support this hypothesis. To examine the effect of CVVH on mortality and other clinically important outcomes compared with CVVHDF in the intensive care unit (ICU) setting. Using a log of all continuous renal replacement therapy performed at a Canadian tertiary centre between 2007 and 2010, the records of patients meeting the inclusion criteria of being admitted to the ICU, and receiving either CVVH or CVVHDF for management of acute renal failure, were reviewed. The information retrieved included demographic data, death events, and hospital and ICU length of stay. Data from 153 patients were included in the present study. Hospital and 30-day mortality were similar in the CVVH and CVVHD...
BMC musculoskeletal disorders, 2014
Individuals with diabetes have been found previously to be at increased risk of non-traumatic fra... more Individuals with diabetes have been found previously to be at increased risk of non-traumatic fracture. However, it is unclear if these individuals are being identified and treated for osteoporosis. 7753 Canadians over 50 years of age were followed prospectively for 10 years. 606/7753 (7.8%) of had diabetes; 98 were insulin-dependent and 508 were not. Using a cox proportional hazards model, we assessed the association between diabetes status and incident non-traumatic fracture. Using logistic regression we identified factors associated with bisphosphonate use over the 10 year period of study. Mean (SD) age of participants was 66.7(9.4) years and 72% were female. Those with diabetes had higher BMD T-scores at baseline, with a mean (SD) femoral neck T-Score of -0.97 (1.06), compared to -1.24 (0.99) in the general cohort. The adjusted hazard ratio (HR) for incident non-traumatic fracture in individuals with insulin-dependent diabetes over the 10 year study period was 2.50 (95% confiden...
Journal of Bone and Mineral Research, 2015
Vertebral fractures are an important yet under-recognized manifestation of osteoporosis in childr... more Vertebral fractures are an important yet under-recognized manifestation of osteoporosis in children with chronic, glucocorticoid-treated illnesses. Our goal was to determine the incidence and clinical predictors of vertebral fractures in the three years following glucocorticoid initiation among pediatric patients with rheumatic disorders. Incident vertebral fractures were evaluated according to the Genant semi-quantitative method on lateral radiographs at baseline and then annually in the 3 years following glucocorticoid initiation. Extended Cox models were used to assess the association between vertebral fractures and clinical risk predictors. 134 children with rheumatic disorders were enrolled in the study (mean ± standard deviation (SD) age 9.9±4.4 years, 65% girls). The unadjusted vertebral fracture incidence rate was 4.4 per 100 person-years, with a three-year incidence proportion of 12.4%. The highest annual incidence occurred in the first year (6.0%, 95% confidence interval (CI) 2.9-11.7). Almost half of the patients with fractures were asymptomatic. Every 0.5 mg/kg increase in average daily glucocorticoid (prednisone equivalents) dose was associated with a 2.0-fold increased fracture risk (hazard ratio (HR) 2.0, 95% CI 1.1-3.5). Other predictors of increased vertebral fracture risk included: (1) Increases in disease severity scores between baseline and 12 months, (2) Increases in body mass index Z-scores in the first 6 of each 12-month period preceding the annual fracture assessment, and (3) Decreases in lumbar spine bone mineral density Z-scores in the first 6 months of glucocorticoid therapy. As such, we observed that a clinically significant number of children with rheumatic disorders developed incident vertebral fractures in the three years following glucocorticoid initiation. Almost half of the children were asymptomatic and thereby would have been undiagnosed in the absence of radiographic monitoring. In addition, discrete clinical predictors of incident vertebral fractures were evident early in the course of glucocorticoid therapy. This article is protected by copyright. All rights reserved.
ISRN Epidemiology, 2013
Objective. Individuals with diabetes have been found to be at increased risk of nontraumatic frac... more Objective. Individuals with diabetes have been found to be at increased risk of nontraumatic fracture. However, within the diabetic population, how to distinguish who is at the highest risk and warranting therapy has remained elusive. Design. Cross-sectional analysis of a national population-based cohort study. Patients. Men and women over the age of 50 with diabetes from across Canada. Measurements. Logistic regression analysis to identify diabetes specific factors associated with a history of one or more nontraumatic fractures. Results. Six hundred and six individuals with diabetes with a mean age of 69 years were examined. Thirty percent had a history of non-traumatic fracture. Macrovascular diseases in the form of stroke or TIA, as well as hypertension, were found to be independently associated with fragility fracture. Other, more traditional, clinical risk factors were also associated with fracture, including increased age, female gender, rheumatoid arthritis, family history of osteoporosis, and decreased bone mineral density. Conclusions. In this cohort of Canadians with diabetes, those with rheumatoid arthritis, a family history of osteoporosis, female gender, increased age, decreased BMD, cerebrovascular disease, or hypertension were more likely to have had a non-traumatic fracture. These risk factors may be important to clinicians when identifying which of their diabetic patients are at highest risk of fracture and in need of preventative therapies.
Open Access Medical Statistics, 2012
Introduction: Although researchers have proposed various strategies to handle missing outcomes in... more Introduction: Although researchers have proposed various strategies to handle missing outcomes in cluster randomized trials (CRTs), limited attention has been paid to the performance of these strategies. Under the assumption of covariate-dependent missingness, the objective of this simulation study is to compare the performance of various strategies in handling missing binary outcomes in CRTs under different design settings. Methods: There are six missing data strategies investigated in this paper, which include complete case analysis, standard multiple imputation (MI) strategies using either logistic regression or Markov chain Monte Carlo (MCMC) method, within-cluster MI strategies using either logistic regression or MCMC method, and MI using logistic regression with cluster as a fixed effect. The performance of these strategies is evaluated through bias, empirical standard error, root mean squared error, and coverage probability. Results: Under the assumption of covariate-dependent missingness and applying the generalized estimating equations approach for fitting the logistic regression, it was shown that complete case analysis yields valid inferences when the percentage of missing outcomes is not large (,20%) for all the designs of CRTs considered in this paper. Standard MI strategies can be adopted when the design effect is small (variance inflation factor [VIF] # 3); however, they tend to underestimate the standard error of treatment effect when the design effect is large. Within-cluster MI strategy using logistic regression is valid for imputation of missing data from CRTs, especially when the cluster size is large (.50) and the design effect is large (VIF . 3). In contrast, within-cluster MI strategy using MCMC method may yield biased estimates of treatment effect for CRTs with small cluster size (#50). MI using logistic regression with cluster as a fixed effect may substantially overestimate the standard error of the estimated treatment effect when the intracluster correlation coefficient is small. It may also lead to biased estimated treatment effect. Conclusion: Findings from this simulation study provide researchers with quantitative evidence to guide selection of an appropriate strategy to deal with missing binary outcomes.
The Journal of Clinical Endocrinology & Metabolism, 2014
Our objectives were to assess the magnitude of the disparity in lumbar spine bone mineral density... more Our objectives were to assess the magnitude of the disparity in lumbar spine bone mineral density (LSBMD) Z-scores generated by different reference databases and to evaluate whether the relationship between LSBMD Z-scores and vertebral fractures (VF) varies by choice of database. Children with leukemia underwent LSBMD by cross-calibrated dual-energy x-ray absorptiometry, with Z-scores generated according to Hologic and Lunar databases. VF were assessed by the Genant method on spine radiographs. Logistic regression was used to assess the association between fractures and LSBMD Z-scores. Net reclassification improvement and area under the receiver operating characteristic curve were calculated to assess the predictive accuracy of LSBMD Z-scores for VF. For the 186 children from 0 to 18 years of age, 6 different age ranges were studied. The Z-scores generated for the 0 to 18 group were highly correlated (r ≥ 0.90), but the proportion of children with LSBMD Z-scores ≤-2.0 among those with VF varied substantially (from 38-66%). Odds ratios (OR) for the association between LSBMD Z-score and VF were similar regardless of database (OR = 1.92, 95% confidence interval 1.44, 2.56 to OR = 2.70, 95% confidence interval 1.70, 4.28). Area under the receiver operating characteristic curve and net reclassification improvement ranged from 0.71 to 0.75 and -0.15 to 0.07, respectively. Although the use of a LSBMD Z-score threshold as part of the definition of osteoporosis in a child with VF does not appear valid, the study of relationships between BMD and VF is valid regardless of the BMD database that is used.
Canadian Journal of Anesthesia/Journal canadien d'anesthésie, 2013
Purpose The primary objectives of this historical casecontrol study were to evaluate the incidenc... more Purpose The primary objectives of this historical casecontrol study were to evaluate the incidence of and reasons and risk factors for adult unanticipated admissions in three tertiary care Canadian hospitals following ambulatory surgery. Methods A random sample of 200 patients requiring admission (cases) and 200 patients not requiring admission (controls) was taken from 20,657 ambulatory procedures was identified and compared. The following variables were included: demographics, reason for admission, type of anesthesia, surgical procedure, length of procedure, American Society of Anesthesiologists' (ASA) classification, surgical completion time, pre-anesthesia clinic, medical history, medications (classes), and perioperative complications. Multiple logistic regression analysis was used to assess factors associated with unanticipated admissions.
BMC Medical Research Methodology, 2009
Background: Cluster randomized trials (CRTs) are increasingly used to assess the effectiveness of... more Background: Cluster randomized trials (CRTs) are increasingly used to assess the effectiveness of interventions to improve health outcomes or prevent diseases. However, the efficiency and consistency of using different analytical methods in the analysis of binary outcome have received little attention. We described and compared various statistical approaches in the analysis of CRTs using the Community Hypertension Assessment Trial (CHAT) as an example. The CHAT study was a cluster randomized controlled trial aimed at investigating the effectiveness of pharmacy-based blood pressure clinics led by peer health educators, with feedback to family physicians (CHAT intervention) against Usual Practice model (Control), on the monitoring and management of BP among older adults.
BMC Medical Research Methodology, 2011
Background: Attrition, which leads to missing data, is a common problem in cluster randomized tri... more Background: Attrition, which leads to missing data, is a common problem in cluster randomized trials (CRTs), where groups of patients rather than individuals are randomized. Standard multiple imputation (MI) strategies may not be appropriate to impute missing data from CRTs since they assume independent data. In this paper, under the assumption of missing completely at random and covariate dependent missing, we compared six MI strategies which account for the intra-cluster correlation for missing binary outcomes in CRTs with the standard imputation strategies and complete case analysis approach using a simulation study. Method: We considered three within-cluster and three across-cluster MI strategies for missing binary outcomes in CRTs. The three within-cluster MI strategies are logistic regression method, propensity score method, and Markov chain Monte Carlo (MCMC) method, which apply standard MI strategies within each cluster. The three acrosscluster MI strategies are propensity score method, random-effects (RE) logistic regression approach, and logistic regression with cluster as a fixed effect. Based on the community hypertension assessment trial (CHAT) which has complete data, we designed a simulation study to investigate the performance of above MI strategies. Results: The estimated treatment effect and its 95% confidence interval (CI) from generalized estimating equations (GEE) model based on the CHAT complete dataset are 1.14 (0.76 1.70). When 30% of binary outcome are missing completely at random, a simulation study shows that the estimated treatment effects and the corresponding 95% CIs from GEE model are 1.15 (0.76 1.75) if complete case analysis is used, 1.12 (0.72 1.73) if within-cluster MCMC method is used, 1.21 (0.80 1.81) if across-cluster RE logistic regression is used, and 1.16 (0.82 1.64) if standard logistic regression which does not account for clustering is used. Conclusion: When the percentage of missing data is low or intra-cluster correlation coefficient is small, different approaches for handling missing binary outcome data generate quite similar results. When the percentage of missing data is large, standard MI strategies, which do not take into account the intra-cluster correlation, underestimate the variance of the treatment effect. Within-cluster and across-cluster MI strategies (except for random-effects logistic regression MI strategy), which take the intra-cluster correlation into account, seem to be more appropriate to handle the missing outcome from CRTs. Under the same imputation strategy and percentage of missingness, the estimates of the treatment effect from GEE and RE logistic regression models are similar.
BMC Medical Research Methodology, 2011
Background: Multicentre randomized controlled trials (RCTs) routinely use randomization and analy... more Background: Multicentre randomized controlled trials (RCTs) routinely use randomization and analysis stratified by centre to control for differences between centres and to improve precision. No consensus has been reached on how to best analyze correlated continuous outcomes in such settings. Our objective was to investigate the properties of commonly used statistical models at various levels of clustering in the context of multicentre RCTs. Methods: Assuming no treatment by centre interaction, we compared six methods (ignoring centre effects, including centres as fixed effects, including centres as random effects, generalized estimating equation (GEE), and fixed-and random-effects centre-level analysis) to analyze continuous outcomes in multicentre RCTs using simulations over a wide spectrum of intraclass correlation (ICC) values, and varying numbers of centres and centre size. The performance of models was evaluated in terms of bias, precision, mean squared error of the point estimator of treatment effect, empirical coverage of the 95% confidence interval, and statistical power of the procedure. Results: While all methods yielded unbiased estimates of treatment effect, ignoring centres led to inflation of standard error and loss of statistical power when within centre correlation was present. Mixed-effects model was most efficient and attained nominal coverage of 95% and 90% power in almost all scenarios. Fixed-effects model was less precise when the number of centres was large and treatment allocation was subject to chance imbalance within centre. GEE approach underestimated standard error of the treatment effect when the number of centres was small. The two centre-level models led to more variable point estimates and relatively low interval coverage or statistical power depending on whether or not heterogeneity of treatment contrasts was considered in the analysis.
BMC Medical Research Methodology, 2013
Background: The objective of this simulation study is to compare the accuracy and efficiency of p... more Background: The objective of this simulation study is to compare the accuracy and efficiency of population-averaged (i.e. generalized estimating equations (GEE)) and cluster-specific (i.e. random-effects logistic regression (RELR)) models for analyzing data from cluster randomized trials (CRTs) with missing binary responses.