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

Using routine inpatient data to identify patients at risk of hospital readmission

Background: A relatively small percentage of patients with chronic medical conditions account for a much larger percentage of inpatient costs. There is some evidence that case-management can improve health and quality-of-life and reduce the number of times these patients are readmitted. To assess whether a statistical algorithm, based on routine inpatient data, can be used to identify patients at risk of readmission and who would therefore benefit from case-management

Living at home after emergency hospital admission:prospective cohort study in older adults with and without cognitive spectrum disorder

Background: Cognitive spectrum disorders (CSDs) are common in hospitalised older adults and associated with adverse outcomes. Their association with the maintenance of independent living has not been established. The aim was to establish the role of CSDs on the likelihood of living at home 30 days after discharge or being newly admitted to a care home. Methods: A prospective cohort study with routine data linkage was conducted based on admissions data from the acute medical unit of a district general hospital in Scotland. 5570 people aged ≥ 65 years admitted from a private residence who survived to discharge and received the Older Persons Routine Acute Assessment (OPRAA) during an incident emergency medical admission were included. The outcome measures were living at home, defined as a private residential address, 30 days after discharge and new care home admission at hospital discharge. Outcomes were ascertained through linkage to routine data sources. Results: Of the 5570 individuals admitted from a private residence who survived to discharge, those without a CSD were more likely to be living at home at 30 days than those with a CSD (93.4% versus 81.7%; difference 11.7%, 95%CI 9.7–13.8%). New discharge to a care home affected 236 (4.2%) of the cohort, 181 (76.7%) of whom had a CSD. Logistic regression modelling identified that all four CSD categories were associated with a reduced likelihood of living at home and an increased likelihood of discharge to a care home. Those with delirium superimposed on dementia were the least likely to be living at home (OR 0.25), followed by those with dementia (OR 0.43), then unspecified cognitive impairment (OR 0.55) and finally delirium (OR 0.57). Conclusions: Individuals with a CSD are at significantly increased risk of not returning home after hospitalisation, and those with CSDs account for the majority of new admissions to care homes on discharge. Individuals with delirium superimposed on dementia are the most affected. We need to understand how to configure and deliver healthcare services to enable older people to remain as independent as possible for as long as possible and to ensure transitions of care are managed supportively

The Sloan Digital Sky Survey Reverberation Mapping Project: Key Results

We present the final data from the Sloan Digital Sky Survey Reverberation Mapping (SDSS-RM) project, a precursor to the SDSS-V Black Hole Mapper Reverberation Mapping program. This data set includes 11-year photometric and 7-year spectroscopic light curves for 849 broad-line quasars over a redshift range of 0.1<z<4.5 and a luminosity range of Lbol=1E44-47.5 erg/s, along with spectral and variability measurements. We report 23, 81, 125, and 110 reverberation mapping lags (relative to optical continuum variability) for broad Halpha, Hbeta, MgII and CIV using the SDSS-RM sample, spanning much of the luminosity and redshift ranges of the sample. Using 30 low-redshift RM AGNs with dynamical-modeling black hole masses, we derive a new estimate of the average virial factor of =0.62+-0.07 for the line dispersion measured from the RMS spectrum. The intrinsic scatter of individual virial factors is 0.31+-0.07 dex, indicating a factor of two systematic uncertainty in RM black hole masses. Our lag measurements reveal significant R-L relations for Hbeta and MgII at high redshift, consistent with the latest measurements based on heterogeneous samples. While we are unable to robustly constrain the slope of the R-L relation for CIV given the limited dynamical range in luminosity, we found substantially larger scatter in CIV lags at fixed L1350. Using the SDSS-RM lag sample, we derive improved single-epoch (SE) mass recipes for Hbeta, MgII and CIV, which are consistent with their respective RM masses as well as between the SE recipes from two different lines, over the luminosity range probed by our sample. The new Hbeta and MgII recipes are approximately unbiased estimators at given RM masses, but there are systematic biases in the CIV recipe. The intrinsic scatter of SE masses around RM masses is ~0.45 dex for Hbeta and MgII, increasing to ~0.58 dex for CIV.Comment: 33 pages. Data products available at ftp://quasar.astro.illinois.edu/public/sdssrm/final_result

Safety and efficacy of fluoxetine on functional outcome after acute stroke (AFFINITY): a randomised, double-blind, placebo-controlled trial

Background Trials of fluoxetine for recovery after stroke report conflicting results. The Assessment oF FluoxetINe In sTroke recoverY (AFFINITY) trial aimed to show if daily oral fluoxetine for 6 months after stroke improves functional outcome in an ethnically diverse population. Methods AFFINITY was a randomised, parallel-group, double-blind, placebo-controlled trial done in 43 hospital stroke units in Australia (n=29), New Zealand (four), and Vietnam (ten). Eligible patients were adults (aged ≥18 years) with a clinical diagnosis of acute stroke in the previous 2–15 days, brain imaging consistent with ischaemic or haemorrhagic stroke, and a persisting neurological deficit that produced a modified Rankin Scale (mRS) score of 1 or more. Patients were randomly assigned 1:1 via a web-based system using a minimisation algorithm to once daily, oral fluoxetine 20 mg capsules or matching placebo for 6 months. Patients, carers, investigators, and outcome assessors were masked to the treatment allocation. The primary outcome was functional status, measured by the mRS, at 6 months. The primary analysis was an ordinal logistic regression of the mRS at 6 months, adjusted for minimisation variables. Primary and safety analyses were done according to the patient's treatment allocation. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12611000774921. Findings Between Jan 11, 2013, and June 30, 2019, 1280 patients were recruited in Australia (n=532), New Zealand (n=42), and Vietnam (n=706), of whom 642 were randomly assigned to fluoxetine and 638 were randomly assigned to placebo. Mean duration of trial treatment was 167 days (SD 48·1). At 6 months, mRS data were available in 624 (97%) patients in the fluoxetine group and 632 (99%) in the placebo group. The distribution of mRS categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio 0·94, 95% CI 0·76–1·15; p=0·53). Compared with patients in the placebo group, patients in the fluoxetine group had more falls (20 [3%] vs seven [1%]; p=0·018), bone fractures (19 [3%] vs six [1%]; p=0·014), and epileptic seizures (ten [2%] vs two [<1%]; p=0·038) at 6 months. Interpretation Oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and epileptic seizures. These results do not support the use of fluoxetine to improve functional outcome after stroke

Health Technology Assessment of Thiopurine Methyltransferase Testing for Guiding 6-mercaptopurine Doses in Paediatric Patients with Acute Lymphoblastic Leukemia

Produced by Technology Assessment at SickKids, Hospital for Sick Children.During the final maintenance phase of therapy for childhood leukemia, an immunosuppressive agent called 6-mercaptopurine (6-MP) is used. The risks of certain adverse drug events (ADE) as a result of 6-MP-treatment are influenced by genetic variations within the population in the enzyme responsible for metabolizing 6-MP, thiopurine methyltransferase (TPMT). There are currently two methods of detecting TPMT enzyme deficiency: a phenotype test (enzymatic assay) that gives a metabolite activity reading and a genotype test that detects the presence of mutations in the genes responsible for producing the TPMT enzyme. Given the high cost of genetic testing and the importance of preventing ADEs, understanding the incremental cost-effectiveness of either form of testing compared to standard care (no testing) would be valuable to guide therapy. The primary objective was to review the literature systematically to determine the accuracy of TPMT phenotype and and genotype tests. The secondary objective was to determine the incremental cost of TPMT genotyping and phenotyping compared to standard weight-based dosing strategies per life-month saved.Supported by the Atlantic Canada Opportunities Agency, the Government of Newfoundland and Labrador, Memorial University of Newfoundland, the Ontario Ministry of Health and Long-Term Care Drug Innovation Fund, and the Newfoundland and Labrador Centre for Health Information

Examining attributes of retailers that influence where cannabis is purchased: a discrete choice experiment

Abstract Background With the legalization of cannabis in Canada, consumers are presented with numerous purchase options. Licensed retailers are limited by the Cannabis Act and provincial regulations with respect to offering sales, advertising, location, maximum quantities, and information sharing in an effort to protect public health and safety. The degree these policies influence consumer purchase behavior will help inform regulatory refinement. Methods A discrete choice experiment within a cross-sectional online survey was used to explore trade-offs consumers make when deciding where to purchase cannabis. Attributes included availability of sales/discounts, proximity, product information, customer service, product variety, and provincial regulation. Participants ≥ 19 years old who lived in Canada and purchased cannabis in the previous 12 months were recruited through an online market research survey panel. A multinomial logit (MNL) model was used for the base model, and latent class analysis was used to assess preference sub-groups. Key limitations included ordering effect, hypothetical bias, and framing effect. Results The survey was completed by 1626 people, and the base model showed that customer service carried the most weight in purchase decisions, followed by proximity and availability of sales and discounts. There was considerable heterogeneity in preference patterns, with a five-group latent class model demonstrating best fit. Only one group (15% of sample) placed a high value on the store being provincially regulated, while three groups were willing to make a trade-off with regulation to access better customer service, product information, or closer proximity. One group preferred non-regulated sources (24% of sample); this group was also primarily driven by the availability of sales and discounts. Three groups (60.5% of sample) preferred online stores. Conclusion This study highlighted that there exists significant diversity with respect to the influence of consumer experiences on cannabis purchase behaviors. Modifications to cannabis retail regulations that focus on improving access to product information as well as reviewing limitations on sales and discounts could have the most impact for shifting customers to licensed retailers

Additional file 1 of Examining attributes of retailers that influence where cannabis is purchased: a discrete choice experiment

Additional file 1