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  • 1
    In: BMC Health Services Research, Springer Science and Business Media LLC, Vol. 21, No. 1 ( 2021-12)
    Abstract: Cardiovascular death is a common outcome in population-based studies about new healthcare interventions or treatments, such as new prescription medications. Vital statistics registration systems are often the preferred source of information about cause-specific mortality because they capture verified information about the deceased, but they may not always be accessible for linkage with other sources of population-based data. We assessed the validity of an algorithm applied to administrative health records for identifying cardiovascular deaths in population-based data. Methods Administrative health records were from an existing multi-database cohort study about sodium-glucose cotransporter-2 (SGLT2) inhibitors, a new class of antidiabetic medications. Data were from 2013 to 2018 for five Canadian provinces (Alberta, British Columbia, Manitoba, Ontario, Quebec) and the United Kingdom (UK) Clinical Practice Research Datalink (CPRD). The cardiovascular mortality algorithm was based on in-hospital cardiovascular deaths identified from diagnosis codes and select out-of-hospital deaths. Sensitivity, specificity, and positive and negative predictive values (PPV, NPV) were calculated for the cardiovascular mortality algorithm using vital statistics registrations as the reference standard. Overall and stratified estimates and 95% confidence intervals (CIs) were computed; the latter were produced by site, location of death, sex, and age. Results The cohort included 20,607 individuals (58.3% male; 77.2% ≥70 years). When compared to vital statistics registrations, the cardiovascular mortality algorithm had overall sensitivity of 64.8% (95% CI 63.6, 66.0); site-specific estimates ranged from 54.8 to 87.3%. Overall specificity was 74.9% (95% CI 74.1, 75.6) and overall PPV was 54.5% (95% CI 53.7, 55.3), while site-specific PPV ranged from 33.9 to 72.8%. The cardiovascular mortality algorithm had sensitivity of 57.1% (95% CI 55.4, 58.8) for in-hospital deaths and 72.3% (95% CI 70.8, 73.9) for out-of-hospital deaths; specificity was 88.8% (95% CI 88.1, 89.5) for in-hospital deaths and 58.5% (95% CI 57.3, 59.7) for out-of-hospital deaths. Conclusions A cardiovascular mortality algorithm applied to administrative health records had moderate validity when compared to vital statistics data. Substantial variation existed across study sites representing different geographic locations and two healthcare systems. These variations may reflect different diagnostic coding practices and healthcare utilization patterns.
    Type of Medium: Online Resource
    ISSN: 1472-6963
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2050434-2
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  • 2
    In: Diabetes Care, American Diabetes Association, Vol. 43, No. 10 ( 2020-10-01), p. 2444-2452
    Abstract: Reports of amputations associated with sodium–glucose cotransporter 2 (SGLT2) inhibitors have been inconsistent. We aimed to compare the risk of below-knee amputation with SGLT2 inhibitors versus dipeptidyl peptidase 4 (DPP-4) inhibitors among patients with type 2 diabetes. RESEARCH DESIGN AND METHODS This multicenter observational study used administrative health care databases from seven Canadian provinces and the U.K. Incident SGLT2 inhibitor users were matched to DPP-4 inhibitor users using a prevalent new-user design and time-conditional propensity scores. Cox proportional hazards models were used to estimate site-specific adjusted hazard ratios (HR) and corresponding 95% CIs of incident below-knee amputation for SGLT2 inhibitor versus DPP-4 inhibitor users. Random effects meta-analyses were used to pool the site-specific results. RESULTS The study cohort included 207,817 incident SGLT2 inhibitor users matched to 207,817 DPP-4 inhibitor users. During a mean exposed follow-up time of 11 months, the amputation rate was 1.3 per 1,000 person-years among SGLT2 inhibitor users and 1.5 per 1,000 person-years among DPP-4 inhibitor users. The adjusted HR of below-knee amputations associated with SGLT2 inhibitor use compared with DPP-4 inhibitor use was 0.88 (95% CI 0.71–1.09). Similar results were obtained in stratified analyses by specific SGLT2 inhibitor molecule. CONCLUSIONS In this large multicenter observational study, there was no association between SGLT2 inhibitor use and incident below-knee amputations among patients with type 2 diabetes compared with DPP-4 inhibitor use. While these findings provide some reassurance, studies with a longer duration of follow-up are needed to assess potential long-term effects.
    Type of Medium: Online Resource
    ISSN: 0149-5992 , 1935-5548
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2020
    detail.hit.zdb_id: 1490520-6
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  • 3
    In: Journal of Alzheimer's Disease, IOS Press, Vol. 81, No. 1 ( 2021-05-04), p. 329-338
    Abstract: Background: Previous studies suggested a link between various infectious pathogens and the development of Alzheimer’s disease (AD), posing the question whether infectious disease could present a novel modifiable risk factor. Objective: To assess whether infectious disease burden due to clinically apparent infections is associated with an increased risk of AD. Methods: We conducted a population-based nested case-control study using the United Kingdom Clinical Practice Research Datalink. We included all dementia-free subjects ≥50 years of age enrolling in the database between January 1988 and December 2017. Each case of AD identified during follow-up was matched with up to 40 controls. Conditional logistic regression estimated adjusted odds ratios (ORs) with 95% confidence intervals (CIs) of AD associated with ≥1 infection diagnosed 〉  2 years before the index date compared with no infection during the study period. We further stratified by time since first infection and cumulative number of infections. Results: The cohort included overall 4,262,092 individuals (mean age at cohort entry 60.4 years; 52% female). During a median follow-up of 10.5 years, 40,455 cases of AD were matched to 1,610,502 controls. Compared with having no burden of infectious disease, having a burden of infectious disease was associated with an increase in the risk of AD (OR, 1.05; 95% CI, 1.02 to 1.08). The risk increased with longer time since first infection, peaking after 12–30 years (OR, 1.11; 95% CI, 1.05–1.17). The risk did not increase with cumulative number of infections. Conclusion: The overall risk of AD associated with infectious disease burden was small but increased gradually with longer time since first infection.
    Type of Medium: Online Resource
    ISSN: 1387-2877 , 1875-8908
    Language: Unknown
    Publisher: IOS Press
    Publication Date: 2021
    detail.hit.zdb_id: 2070772-1
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  • 4
    In: Annals of Internal Medicine, American College of Physicians, Vol. 173, No. 6 ( 2020-09-15), p. 417-425
    Type of Medium: Online Resource
    ISSN: 0003-4819 , 1539-3704
    RVK:
    Language: English
    Publisher: American College of Physicians
    Publication Date: 2020
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  • 5
    Online Resource
    Online Resource
    Wiley ; 2020
    In:  Diabetes, Obesity and Metabolism Vol. 22, No. 2 ( 2020-02), p. 254-262
    In: Diabetes, Obesity and Metabolism, Wiley, Vol. 22, No. 2 ( 2020-02), p. 254-262
    Abstract: To assess the incidence of cardiovascular and hypoglycaemic adverse events associated with glimepiride compared with other second‐generation sulphonylureas among patients with type 2 diabetes in a real‐world clinical setting. Materials and methods We identified all sulphonylurea initiators between 1998 and 2017 in the UK Clinical Practice Research Datalink. Using a prevalent new‐user design, glimepiride initiators were matched 1:4 with initiators of other second‐generation sulphonylureas on calendar time, prior sulphonylurea use, and time‐conditional high‐dimensional propensity score. Cox proportional hazards models yielded adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for myocardial infarction, ischaemic stroke, severe hypoglycaemia, cardiovascular death, and all‐cause mortality. Results Among 66 032 sulphonylurea new users, 6438 initiated glimepiride and were matched to up to 20 582 initiators of other second‐generation sulphonylureas. During a mean follow‐up of 1.3 years, glimepiride was associated with a similar incidence of myocardial infarction (HR 0.99, 95% CI 0.75–1.30) and ischaemic stroke (HR 0.96, 95% CI 0.72–1.27) compared with other second‐generation sulphonylureas, while there was a non‐significant trend towards a higher incidence of severe hypoglycaemia (HR 1.24, 95% CI 0.92–1.68). Glimepiride was also associated with a lower incidence of all‐cause mortality (HR 0.77, 95% CI 0.67–0.89), and a non‐significant but similar trend for cardiovascular death (HR 0.83, 95% CI 0.65–1.05). Conclusions Glimepiride was associated with a lower incidence of all‐cause mortality compared with other second‐generation sulphonylureas.
    Type of Medium: Online Resource
    ISSN: 1462-8902 , 1463-1326
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2004918-3
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  • 6
    In: BMJ, BMJ
    Abstract: To compare the risk of cardiovascular events between sodium glucose cotransporter 2 (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP-4) inhibitors among people with type 2 diabetes in a real world context of clinical practice. Design Multi-database retrospective cohort study using a prevalent new user design with subsequent meta-analysis. Setting Canadian Network for Observational Drug Effect Studies (CNODES), with administrative healthcare databases from seven Canadian provinces and the United Kingdom, 2013-18. Population 209 867 new users of a SGLT2 inhibitor matched to 209 867 users of a DPP-4 inhibitor on time conditional propensity score and followed for a mean of 0.9 years. Main outcome measures The primary outcome was major adverse cardiovascular events (MACE, a composite of myocardial infarction, ischaemic stroke, or cardiovascular death). Secondary outcomes were the individual components of MACE, heart failure, and all cause mortality. Cox proportional hazards models were used to estimate site specific adjusted hazards ratios and 95% confidence intervals, comparing use of SGLT2 inhibitors with use of DPP-4 inhibitors in an as treated approach. Site specific results were pooled using random effects meta-analysis. Results Compared with DPP-4 inhibitors, SGLT2 inhibitors were associated with decreased risks of MACE (incidence rate per 1000 person years: 11.4 v 16.5; hazard ratio 0.76, 95% confidence interval 0.69 to 0.84), myocardial infarction (5.1 v 6.4; 0.82, 0.70 to 0.96), cardiovascular death (3.9 v 7.7; 0.60, 0.54 to 0.67), heart failure (3.1 v 7.7; 0.43, 0.37 to 0.51), and all cause mortality (8.7 v 17.3; 0.60, 0.54 to 0.67). SGLT2 inhibitors had more modest benefits for ischaemic stroke (2.6 v 3.5; 0.85, 0.72 to 1.01). Similar benefits for MACE were observed with canagliflozin (0.79, 0.66 to 0.94), dapagliflozin (0.73, 0.63 to 0.85), and empagliflozin (0.77, 0.68 to 0.87). Conclusions In this large observational study conducted in a real world clinical practice context, the short term use of SGLT2 inhibitors was associated with a decreased risk of cardiovascular events compared with the use of DPP-4 inhibitors. Trial registration ClinicalTrials.gov NCT03939624 .
    Type of Medium: Online Resource
    ISSN: 1756-1833
    Language: English
    Publisher: BMJ
    Publication Date: 2020
    detail.hit.zdb_id: 1479799-9
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  • 7
    In: Diabetes, Obesity and Metabolism, Wiley, Vol. 22, No. 9 ( 2020-09), p. 1648-1658
    Abstract: To compare urosepsis rates in patients with type 2 diabetes treated using sodium‐glucose co‐transporter‐2 inhibitors (SGLT2i) with dipeptidyl peptidase‐4 inhibitors (DPP4i) in a real‐world setting. Methods We conducted a matched cohort study using a prevalent new‐user design with time‐conditional propensity scores. New users of SGLT2i from seven Canadian provinces and the UK were matched to DPP4i users. The primary outcome was hospitalization with a diagnosis of urosepsis and the secondary outcome was Fournier's gangrene. Site‐specific hazard ratios for urosepsis comparing SGLT2i with DPP4i were estimated using Cox proportional hazards models and pooled using a random effects meta‐analysis. Results We included 208 244 users of SGLT2i and 208 244 users of DPP4i. Among SGLT2i users, 42% initiated canagliflozin, 31% dapagliflozin and 27% empagliflozin. During a mean follow‐up of 0.9 years, patients initiating SGLT2i had a lower rate of urosepsis compared with those receiving DPP4i. The pooled adjusted hazard ratio was 0.58 (95% confidence interval [CI]: 0.42‐0.80). The incidence rates of Fournier's gangrene were numerically similar in SGLT2i (0.08 per 1000 person‐years; 95% CI: 0.05‐0.13) and DPP4i users (0.14; 95% CI: 0.09‐0.21). Conclusions In this large, multi‐site study, we did not observe an increased risk for urosepsis associated with SGLT2i compared with DPP4i among patients with type 2 diabetes in a real‐world setting.
    Type of Medium: Online Resource
    ISSN: 1462-8902 , 1463-1326
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2004918-3
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  • 8
    In: BMJ, BMJ
    Type of Medium: Online Resource
    ISSN: 0959-8138 , 1756-1833
    Language: English
    Publisher: BMJ
    Publication Date: 2018
    detail.hit.zdb_id: 1479799-9
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  • 9
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2019
    In:  Neurology Vol. 93, No. 10 ( 2019-09-03), p. e1010-e1020
    In: Neurology, Ovid Technologies (Wolters Kluwer Health), Vol. 93, No. 10 ( 2019-09-03), p. e1010-e1020
    Abstract: To assess whether use of antidepressants with strong inhibition of serotonin reuptake is associated with a decreased incidence of ischemic stroke and myocardial infarction (MI). Methods We conducted a cohort study using the UK Clinical Practice Research Datalink and considering new users of selective serotonin reuptake inhibitors (SSRIs) or third-generation antidepressants who were ≥18 years of age between 1995 and 2014. Using a nested case-control approach, we matched each case of a first ischemic stroke or MI identified during follow-up with up to 30 controls on age, sex, calendar time, and duration of follow-up. We estimated incidence rate ratios (RRs) and 95% confidence intervals (CIs) of each outcome associated with current use of strong compared with weak inhibitors of serotonin reuptake using conditional logistic regression. Results The cohort included 938,388 incident users of SSRIs (n = 868,755) or third-generation antidepressants (n = 69,633). Mean age at cohort entry was 46 years (64% women). During follow-up, 15,860 cases of ischemic stroke and 8,626 cases of MI were identified and matched to 473,712 and 258,022 controls, respectively. Compared with current use of weak inhibitors of serotonin reuptake, current use of strong inhibitors was associated with a decreased rate of ischemic stroke (RR 0.88, 95% CI 0.80–0.97), but the effect size was smaller in some sensitivity analyses. The rate of MI was similar between strong and weak inhibitors (RR 1.00, 95% CI 0.87–1.15). Conclusion Our large population-based study suggests that antidepressants strongly inhibiting serotonin reuptake may be associated with a small decrease in the rate of ischemic stroke.
    Type of Medium: Online Resource
    ISSN: 0028-3878 , 1526-632X
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2019
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