The risk of fragility fractures in new users of dipeptidyl peptidase-4 inhibitors compared to sulfonylureas and other anti-diabetic drugs: A cohort study

Published by Elsevier via http://dx.doi.org/10.1016/j.ces.2017.10.035 © 2017. This final version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/Aims Mixed evidence exists for the effect of incretin-based therapies on osteoporosis in type-2 diabetes. Therefore, we conducted a cohort study to determine the association between dipeptidyl peptidase-4 (DPP-4) inhibitors and common osteoporotic “fragility fractures” (upper extremity, hip, spine).Methods The UK-based Clinical Practice Research Datalink was used to identify adults without prior fractures receiving a new anti-diabetic drug or a new type-2 diabetes diagnosis between 2007 and 2016. The primary aim was to compare new-users of DPP-4 inhibitors versus new-users of sulfonylureas (SU). The association between DPP-4 inhibitors and incident fractures was estimated using Cox proportional hazards models. Deciles of high-dimensional propensity scores and other anti-diabetic drugs were used as covariates. Results We identified 7993 and 26,636 new-users of DPP-4 inhibitors and SUs, respectively. At cohort entry, the mean age was 58.8, 40% were female, mean diabetes duration was 1.3 years, and 42% had A1c > 9%. Over 9 years (mean follow-up = 1.2 years), the incident rate of fragility fractures was lower among DPP-4 versus SU users (3.0/1000 vs. 5.2/1000 person-years; P-value = 0.007). After adjustment, there was no statistically significant difference in fracture risk (hazard ratio adjusted, aHR = 0.80, 95%CI 0.51–1.24; P-value = 0.3125). In a secondary analysis, DPP-4 inhibitors were not associated with a difference in fracture risk compared to insulin (aHR = 0.91, 95%CI 0.40–2.09); however were associated with a lower fracture risk versus thiazolidinediones (aHR = 0.47, 95%CI 0.26–0.83). Sensitivity analyses supported findings. Conclusions DPP-4 inhibitors are not associated with an increased risk of fragility fractures compared with SUs or insulin; however, are associated with a lower risk versus thiazolidinediones.JMG is supported as a New Investigator Award from the Canadian Institute of Health Research (CIHR) and a Clinician Scientist Award from Diabetes Canada. JRD is supported by a CIHR fellowship in drug safety and effectiveness. SRM holds the Endowed Chair in Patient Health Management supported by the Faculties of Medicine and Dentistry and Pharmacy and Pharmaceutical Sciences at the University of Alberta, Edmonton, Alberta, Canada

Assessment of Variation in the Alberta Context Tool: The Contribution of Unit Level Contextual Factors and Specialty in Canadian Pediatric Acute Care Settings

Background: There are few validated measures of organizational context and none that we located are parsimonious and address modifiable characteristics of context. The Alberta Context Tool (ACT) was developed to meet this need. The instrument assesses 8 dimensions of context, which comprise 10 concepts. The purpose of this paper is to report evidence to further the validity argument for ACT. The specific objectives of this paper are to: (1) examine the extent to which the 10 ACT concepts discriminate between patient care units and (2) identify variables that significantly contribute to between-unit variation for each of the 10 concepts. Methods: 859 professional nurses (844 valid responses) working in medical, surgical and critical care units of 8 Canadian pediatric hospitals completed the ACT. A random intercept, fixed effects hierarchical linear modeling (HLM) strategy was used to quantify and explain variance in the 10 ACT concepts to establish the ACT's ability to discriminate between units. We ran 40 models (a series of 4 models for each of the 10 concepts) in which we systematically assessed the unique contribution (i.e., error variance reduction) of different variables to between-unit variation. First, we constructed a null model in which we quantified the variance overall, in each of the concepts. Then we controlled for the contribution of individual level variables (Model 1). In Model 2, we assessed the contribution of practice specialty (medical, surgical, critical care) to variation since it was central to construction of the sampling frame for the study. Finally, we assessed the contribution of additional unit level variables (Model 3). Results: The null model (unadjusted baseline HLM model) established that there was significant variation between units in each of the 10 ACT concepts (i.e., discrimination between units). When we controlled for individual characteristics, significant variation in the 10 concepts remained. Assessment of the contribution of specialty to between-unit variation enabled us to explain more variance (1.19% to 16.73%) in 6 of the 10 ACT concepts. Finally, when we assessed the unique contribution of the unit level variables available to us, we were able to explain additional variance (15.91% to 73.25%) in 7 of the 10 ACT concepts. Conclusion: The findings reported here represent the third published argument for validity of the ACT and adds to the evidence supporting its use to discriminate patient care units by all 10 contextual factors. We found evidence of relationships between a variety of individual and unit-level variables that explained much of this between-unit variation for each of the 10 ACT concepts. Future research will include examination of the relationships between the ACT's contextual factors and research utilization by nurses and ultimately the relationships between context, research utilization, and outcomes for patients

Impact of Body Mass Index on Short-Term Outcomes in Patients Undergoing Percutaneous Coronary Intervention in Newfoundland and Labrador, Canada

Background and Aim. Obesity (BMI ≥ 30 kg/m2) is associated with advanced cardiovascular disease requiring procedures such as percutaneous coronary intervention (PCI). Studies report better outcomes in obese patients having these procedures but results are conflicting or inconsistent. Newfoundland and Labrador (NL) has the highest rate of obesity in Canada. The aim of the study was to examine the relationship between BMI and vascular and nonvascular complications in patients undergoing PCI in NL. Methods. We studied 6473 patients identified in the APPROACH-NL database who underwent PCI from May 2006 to December 2013. BMI categories included normal, 18.5 ≤ BMI < 25.0 (n=1073); overweight, 25.0 ≤ BMI < 30 (n=2608); and obese, BMI ≥ 30.0 (n=2792). Results. Patients with obesity were younger and had a higher incidence of diabetes, hypertension, and family history of cardiac disease. Obese patients experienced less vascular complications (normal, overweight, and obese: 8.2%, 7.2%, and 5.3%, p=0.001). No significant differences were observed for in-lab (4.0%, 3.3%, and 3.1%, p=0.386) or postprocedural (1.0%, 0.8%, and 0.9%, p=0.725) nonvascular complications. After adjusting for covariates, BMI was not a significant factor associated with adverse outcomes. Conclusion. Overweight and obesity were not independent correlates of short-term vascular and nonvascular complications among patients undergoing PCI

Infant feeding mode predicts the costs of healthcare services in one region of Canada: a data linkage pilot study

Objective: The aim is to perform a pilot study evaluating the differences in healthcare service use and its associated costs by infant feeding mode in an infant’s first year of life. Data from a prospective cohort study and administrative databases were linked to examine healthcare use in healthy full term infants (N = 160). Exposure was categorized as exclusively breastfed, mixed fed and exclusively formula fed. Outcomes included hospitalizations, emergency room and physician visits. Descriptive statistics and generalized linear modelling were performed. Results: Overall $315,235 was spent on healthcare service use for the sample of infants during their first year of life. When compared to exclusive breastfeeding, mixed feeding and exclusive formula feeding were found to be significant predictors of total healthcare service use costs (p < 0.05), driven by costs of hospital admissions. Due to the human and economic burden associated with not breastfeeding, policies and programs that support and encourage breastfeeding should be priority

Maternal TLR signaling is required for prenatal asthma protection by the nonpathogenic microbe Acinetobacter lwoffii F78

The pre- and postnatal environment may represent a window of opportunity for allergy and asthma prevention, and the hygiene hypothesis implies that microbial agents may play an important role in this regard. Using the cowshed-derived bacterium Acinetobacter lwoffii F78 together with a mouse model of experimental allergic airway inflammation, this study investigated the hygiene hypothesis, maternal (prenatal) microbial exposure, and the involvement of Toll-like receptor (TLR) signaling in prenatal protection from asthma. Maternal intranasal exposure to A. lwoffii F78 protected against the development of experimental asthma in the progeny. Maternally, A. lwoffii F78 exposure resulted in a transient increase in lung and serum proinflammatory cytokine production and up-regulation of lung TLR messenger RNA. Conversely, suppression of TLRs was observed in placental tissue. To investigate further, the functional relevance of maternal TLR signaling was tested in TLR2/3/4/7/9−/− knockout mice. The asthma-preventive effect was completely abolished in heterozygous offspring from A. lwoffii F78–treated TLR2/3/4/7/9−/− homozygous mother mice. Furthermore, the mild local and systemic inflammatory response was also absent in these A. lwoffii F78–exposed mothers. These data establish a direct relationship between maternal bacterial exposures, functional maternal TLR signaling, and asthma protection in the progeny

Assessment of variation in the alberta context tool: the contribution of unit level contextual factors and specialty in Canadian pediatric acute care settings

Background: There are few validated measures of organizational context and none that we located are parsimonious and address modifiable characteristics of context. The Alberta Context Tool (ACT) was developed to meet this need. The instrument assesses 8 dimensions of context, which comprise 10 concepts. The purpose of this paper is to report evidence to further the validity argument for ACT. The specific objectives of this paper are to: (1) examine the extent to which the 10 ACT concepts discriminate between patient care units and (2) identify variables that significantly contribute to between-unit variation for each of the 10 concepts. Methods: 859 professional nurses (844 valid responses) working in medical, surgical and critical care units of 8 Canadian pediatric hospitals completed the ACT. A random intercept, fixed effects hierarchical linear modeling (HLM) strategy was used to quantify and explain variance in the 10 ACT concepts to establish the ACT’s ability to discriminate between units. We ran 40 models (a series of 4 models for each of the 10 concepts) in which we systematically assessed the unique contribution (i.e., error variance reduction) of different variables to between-unit variation. First, we constructed a null model in which we quantified the variance overall, in each of the concepts. Then we controlled for the contribution of individual level variables (Model 1). In Model 2, we assessed the contribution of practice specialty (medical, surgical, critical care) to variation since it was central to construction of the sampling frame for the study. Finally, we assessed the contribution of additional unit level variables (Model 3). Results: The null model (unadjusted baseline HLM model) established that there was significant variation between units in each of the 10 ACT concepts (i.e., discrimination between units). When we controlled for individual characteristics, significant variation in the 10 concepts remained. Assessment of the contribution of specialty to between-unit variation enabled us to explain more variance (1.19% to 16.73%) in 6 of the 10 ACT concepts. Finally, when we assessed the unique contribution of the unit level variables available to us, we were able to explain additional variance (15.91% to 73.25%) in 7 of the 10 ACT concepts. Conclusion: The findings reported here represent the third published argument for validity of the ACT and adds to the evidence supporting its use to discriminate patient care units by all 10 contextual factors. We found evidence of relationships between a variety of individual and unit-level variables that explained much of this between-unit variation for each of the 10 ACT concepts. Future research will include examination of the relationships between the ACT’s contextual factors and research utilization by nurses and ultimately the relationships between context, research utilization, and outcomes for patients

Patterns and Correlates of Cannabis Use among Individuals with HIV/AIDS in Maritime Canada

BACKGROUND: The prevalence of cannabis use in HIV-infected individuals is high and its long-term effects are unclear. METHODS: The prevalence, perceived benefits and consequences, and predictors of cannabis use were studied using a cross-sectional survey in two immunodeficiency clinics in Maritime Canada. RESULTS: Current cannabis use was identified in 38.5% (87 of 226) of participants. Almost all cannabis users (85 of 87 [97.7%]) acknowledged its use for recreational purposes, with 21.8% (19 of 87) reporting medicinal cannabis use. The majority of patients enrolled in the present study reported mild or no symptoms related to HIV (n=179). Overall, 80.5% (70 of 87) of the cannabis-using participants reported a symptom-relieving benefit, mostly for relief of stress, anorexia or pain. Participants consumed a mean (± SD) of 18.3±21.1 g of cannabis per month and spent an average of $105.15±109.87 on cannabis per month. Cannabis use was associated with rural residence, lower income level, driving under the influence of a substance, and consumption of ecstasy and tobacco. Income level, ecstasy use and tobacco use were retained as significant predictors in regression modelling. Cannabis use was not associated with adverse psychological outcomes. DISCUSSION: Prolonged previous cannabis consumption and the substantial overlap between recreational and medicinal cannabis use highlight the challenges in obtaining a tenable definition of medicinal cannabis therapy

A Randomized Controlled Trial of Four Precolonoscopy Bowel Cleansing Regimens

BACKGROUND: The ideal bowel cleansing regimen for colonoscopy has yet to be determined. OBJECTIVE: To compare the cleansing efficacy, and patient tolerability and safety of four bowel preparation regimens. METHODS: A total of 834 patients undergoing outpatient colonoscopy were randomly assigned to one of four regimens: 4 L polyethylene glycol (PEG); 2 L PEG + 20 mg bisacodyl; 90 mL of sodium phosphate (NaP); or two sachets of a commercially available bowel cleansing solution (PSMC) + 300 mL of magnesium citrate (M). The primary outcome measure was cleansing efficacy, which was scored by blinded endoscopists using the Ottawa Bowel Preparation Scale. Secondary outcome measures were bowel preparation quality according to time of colonoscopy, and patient tolerability and safety. RESULTS: The mean total cleansing score was significantly worse in the NaP group compared with the other three groups (P<0.0001). The mean cleansing scores were worse in patients who underwent morning versus afternoon colonoscopy, a finding that was consistent in all four groups. PSMC + M was the best tolerated regimen. No clinically significant mean changes in creatinine or electrolyte levels were identified, although a significantly higher proportion of patients in the NaP group developed hypokelemia (P<0.0001). CONCLUSIONS: 2 L PEG + 20 mg bisacodyl, or PSMC + M was as efficacious as 4 L PEG and superior to NaP for bowel cleansing. A short interval between the completion of bowel preparation and the start of colonoscopy (ie, ‘runway time’), irrespective of bowel preparation regimen, appeared to be a more important predictor of bowel cleanliness than the cathartic agents used