Association between diabetes and haematological malignancies: a population-based study.

AIMS/HYPOTHESIS: Contemporary data for the association of diabetes with haematological malignancies are lacking. We evaluated the risk of developing haematological malignancies and subsequent mortality in individuals with diabetes compared with those without diabetes. METHODS: We conducted a population-based observational study using healthcare databases from Ontario, Canada. All Ontario residents 30 years of age or older free of cancer and diabetes between 1 January 1996 and 31 December 2015 were eligible for inclusion. Using Cox regression analyses, we explored the association between diabetes and the risk and mortality of haematological malignancies (leukaemia, lymphoma, multiple myeloma). The impact of timing on associations was evaluated with analyses stratified by time since diabetes diagnosis (<3 months, 3 months to 1 year, ≥1 year). RESULTS: We identified 1,003,276 individuals with diabetes and age and sex matched these to 2,006,552 individuals without diabetes. Compared with individuals without diabetes, those with diabetes had a modest but significantly higher risk of a haematological malignancy (adjusted HR 1.10 [95% CI 1.08, 1.12] p < 0.0001). This association persisted across all time periods since diabetes diagnosis. Among those with haematological malignancies, diabetes was associated with a higher all-cause mortality (HR 1.36 [95% CI 1.31, 1.41] p < 0.0001) compared with no diabetes, as well as cause-specific mortality. CONCLUSIONS/INTERPRETATION: Diabetes is associated with a higher risk of haematological malignancies and is an independent risk factor of all-cause and cause-specific mortality. Greater efforts for lifestyle modification may not only reduce diabetes burden and its complications but may also potentially lower risk of malignancy and mortality. Graphical abstract.

Potential diabetes overtreatment and risk of adverse events among older adults in Ontario: a population-based study.

AIMS/HYPOTHESIS: More than 25% of older adults (age ≥75 years) have diabetes and may be at risk of adverse events related to treatment. The aim of this study was to assess the prevalence of intensive glycaemic control in this group, potential overtreatment among older adults and the impact of overtreatment on the risk of serious events. METHODS: We conducted a retrospective, population-based cohort study of community-dwelling older adults in Ontario using administrative data. Participants were ≥75 years of age with diagnosed diabetes treated with at least one anti-hyperglycaemic agent between 2014 and 2015. Individuals were categorised as having intensive or conservative glycaemic control (HbA1c <53 mmol/mol [<7%] or 54-69 mmol/mol [7.1-8.5%], respectively), and as undergoing treatment with high-risk (i.e. insulin, sulfonylureas) or low-risk (other) agents. We measured the composite risk of emergency department visits, hospitalisations, or death within 30 days of reaching intensive glycaemic control with high-risk agents. RESULTS: Among 108,620 older adults with diagnosed diabetes in Ontario, the mean (± SD) age was 80.6 (±4.5) years, 49.7% were female, and mean (± SD) diabetes duration was 13.7 (±6.3) years. Overall, 61% of individuals were treated to intensive glycaemic control and 21.6% were treated to intensive control using high-risk agents. Using inverse probability treatment weighting with propensity scores, intensive control with high-risk agents was associated with nearly 50% increased risk of the composite outcome compared with conservative glycaemic control with low-risk agents (RR 1.49, 95% CI 1.08, 2.05). CONCLUSIONS/INTERPRETATION: Our findings underscore the need to re-evaluate glycaemic targets in older adults and to reconsider the use of anti-hyperglycaemic medications that may lead to hypoglycaemia, especially in setting of intensive glycaemic control.

Levothyroxine dose and risk of atrial fibrillation: A nested case-control study.

Contemporary data on the effect of levothyroxine dose on the occurrence of atrial fibrillation (AF) are lacking, particularly in the older population. Our objective was to determine the effect of cumulative levothyroxine exposure on risk of AF and ischemic stroke in older adults. METHODS: We conducted a population-based observational study using health care databases from Ontario, Canada. We identified adults aged ≥66 years without a history of AF who filled at least 1 levothyroxine prescription between April 1, 2007, and March 31, 2016. Cases were defined as cohort members who had incident AF (emergency room visit or hospitalization) between the date of first levothyroxine prescription and December 31, 2017. Index date was date of AF. Cases were matched with up to 5 controls without AF on the same index date. Secondary outcome was ischemic stroke. Cumulative levothyroxine exposure was estimated based on total milligrams of levothyroxine dispensed in the year prior to index date. Using nested case-control approach, we compared outcomes between older adults who received high (≥0.125 mg/d), medium (0.075-0.125 mg/d), or low (0-0.075 mg/d) cumulative levothyroxine dose. We compared outcomes between current, recent past, and remote past levothyroxine use. RESULTS: Of 183,360 older adults treated with levothyroxine (mean age 82 years; 72% women), 30,560 (16.1%) had an episode of AF. Compared to low levothyroxine exposure, high and medium exposure was associated with significantly increased risk of AF after adjustment for covariates (adjusted odds ratio [aOR] 1.29, 95% CI 1.23-1.35; aOR 1.08, 95% CI 1.04-1.11; respectively). No association was observed between levothyroxine exposure and ischemic stroke. Compared with current levothyroxine use, older adults with remote levothyroxine use had lower risks of AF (aOR 0.56, 95% CI 0.52-0.59) and ischemic stroke (aOR 0.61, 95% CI 0.56-0.67). CONCLUSIONS: Among older persons treated with levothyroxine, levothyroxine at doses >0.075 mg/d is associated with an increased risk of AF compared to lower exposure.

Breast, cervical and colorectal cancer screening in adults with diabetes: a systematic review and meta-analysis.

AIMS/HYPOTHESIS: Individuals with diabetes are at increased risk of developing and dying from cancer. Evidence-based guidelines recommend universal screening for breast, cervical and colorectal cancer; however, evidence on the uptake of these tests in individuals with diabetes is mixed. We conducted a meta-analysis to quantify the association between diabetes and participation in breast, cervical and colorectal cancer screening. METHODS: MEDLINE, EMBASE and CINAHL were searched systematically for publications between 1 January 1997 and 18 July 2018. The search was supplemented by handsearching of reference lists of the included studies and known literature reviews. Abstracts and full texts were assessed in duplicate according to the following eligibility criteria: study conducted in the general population; diabetes included as a predictor vs a comparison group without diabetes; and breast (mammography), cervical (Papanicolaou smear) or colorectal (faecal and endoscopic tests) cancer screening uptake included as an outcome. Random-effects meta-analyses were performed using the most-adjusted estimates for each cancer site. RESULTS: Thirty-seven studies (25 cross-sectional, 12 cohorts) were included, with 27 studies on breast, 19 on cervical and 18 on colorectal cancer screening. Having diabetes was associated with significantly lower likelihood of breast (adjusted OR 0.83 [95% CI 0.77, 0.90]) and cervical (OR 0.76 [95% CI 0.71, 0.81]) cancer screening, relative to not having diabetes. Colorectal cancer screening was comparable across groups with and without diabetes (OR 0.95 [95% CI 0.86, 1.06]); however, women with diabetes were less likely to receive a colorectal cancer screening test than women without diabetes (OR 0.86 [95% CI 0.77, 0.97]). CONCLUSIONS/INTERPRETATION: Our findings suggest that women with diabetes have suboptimal breast, cervical and colorectal cancer screening rates, compared with women without diabetes, although the absolute differences might be modest. Given the increased risk of cancer in this population, higher quality prospective evidence is necessary to evaluate the contribution of diabetes to cancer screening disparities in relation to other patient-, provider- and system-level factors. REGISTRATION: PROSPERO registration ID CRD42017073107.

Sodium glucose cotransporter 2 inhibitors and risk of genital mycotic and urinary tract infection: A population-based study of older women and men with diabetes.

AIMS: The objective of the study was to quantify the association between SGLT2 inhibitors and genital mycotic infection and between SGLT2 inhibitors and urinary tract infection (UTI) within 30 days of drug initiation among older women and men. MATERIALS AND METHODS: This was a retrospective cohort study using linked administrative databases of women and men with diabetes, aged 66 years or older, in Ontario, Canada. We compared the incidence of genital mycotic infection or UTI within 30 days between new users of an SGLT2 inhibitor and of a dipeptidyl-peptidase-4 (DPP4) inhibitor. RESULTS: We identified 21 444 incident users of SGLT2 inhibitor and 22 463 incident users of DPP4 inhibitor. Among SGLT2 inhibitor users, there were 8848 (41%) women and the mean age at index was 71.8 ± 5 (SD) years. After adjusting for propensity score, age, sex and recent UTI, there was a 2.47-fold increased risk of genital mycotic infection with incident use of SGLT2 inhibitors (adjusted hazard ratio (HR), 2.47; 95% confidence interval (CI), 2.08-2.92; P < 0.001) within 30 days compared to incident use of DPP4 inhibitors. For UTI, the adjusted HR was 0.89 (95% CI, 0.78-1.00; P = 0.05). CONCLUSIONS: Incident use of SGLT2 inhibitors among older women and men is associated with increased risk of genital mycotic infections within 30 days; there is no associated increased risk of UTI. These findings from a real-world setting provide evidence of the potential harms of SGLT2 inhibitors.

Delaying Thyroxine Until Positive Beta-Human Chorionic Gonadotropin is Safe for Patients Receiving Fertility Therapy: Applying New ATA Guidelines to Subclinical Hypothyroidism.

OBJECTIVE: This study sought to examine the effect of changing TSH threshold recommendations from 2.5 to 4 mIU/L before fertility therapy on the prevalence of early gestational subclinical hypothyroidism (SCH) (TSH2 >2.5 mIU/L) and to evaluate implications on progression to clinical pregnancy (defined as detection of cardiac activity on ultrasound). METHODS: A retrospective chart review was performed in an academic fertility clinic on all patients with a measured pre-treatment TSH (TSH1) and positive beta-human chorionic gonadotropin following fertility treatment. The study assessed the effect of TSH2 on ongoing pregnancy, both in patients newly diagnosed with SCH and in patients previously receiving LT4, stratified by initial TSH. RESULTS: Of 482 women included in the study, baseline TSH (TSH1) was <2.5 mIU/L in 333 women (69%) and 2.5-4 mIU/L in 64 women (13.2%). Eighty-five women were taking LT4 at baseline (17.6%). Among women with a TSH1 between 2.5 and 4 mIU/L, the corresponding TSH in early pregnancy (TSH2) was <2.5 mIU/L in 35 women (55%). Overall, there was no difference in progression to clinical pregnancy between women with a TSH2 of 2.5-4 mIU/L compared with women with a TSH2 <2.5 mIU/L (OR 0.70; 95% CI 0.44-1.09). Similarly, when excluding women taking LT4 at baseline, there was no difference in progression to clinical pregnancy (OR 0.90; 95% CI 0.28-2.86). CONCLUSION: Rate of progression to clinical pregnancy was equivalent between women with an early pregnancy TSH (TSH2) <2.5 and women with a TSH2 of 2.5-4.0 mIU/L. Our findings support initiating LT4 in early pregnancy, as opposed to pre-pregnancy if the TSH remains above cut-off because there does not appear to be a difference in in early pregnancy outcomes if treatment is delayed.

The temporal relationship between diabetes and cancer: A population-based study.

BACKGROUND: Diabetes is associated with an increased risk of several cancers; however, greater detection of cancer around the time of diabetes diagnosis may partly contribute to this relationship. The goal of the current study was to explore the temporal relationship between diabetes and cancer incidence. METHODS: The authors conducted a retrospective, population-based cohort study of >1 million adults living in Ontario, Canada to evaluate the association between diabetes diagnosis and the incidence of cancer in 3 time periods: within the 10 years before a diabetes diagnosis, within the first 3 months after a diabetes diagnosis, and from 3 months to 10 years after a diabetes diagnosis. RESULTS: Individuals with diabetes were significantly more likely to have been diagnosed with cancer within the 10 years before a diabetes diagnosis compared with individuals without diabetes (odds ratio, 1.23; 95% confidence interval [95% CI], 1.19-1.27). Cancer incidence also was found to be significantly higher in individuals with diabetes within the 3-month period after a diabetes diagnosis (hazard ratio, 1.62; 95% CI, 1.52-1.74), whereas the risk was not found to be elevated in the later period (hazard ratio, 0.97; 95% CI, 0.95-0.98). Similar trends were noted for individual cancers. CONCLUSIONS: The results demonstrated that individuals with diabetes had a significantly higher risk of most cancers, which was limited to the time periods before and immediately after a diabetes diagnosis. The highest risk period was observed within the first 3 months after a diabetes diagnosis, suggesting a partial role of detection bias in the apparent relationship between diabetes and cancer. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2731-2738. © 2016 American Cancer Society.

Risk of Breast Cancer After Diabetes in Pregnancy: A Population-based Cohort Study.

OBJECTIVES: Diabetes is associated with an increased risk of several cancers, including postmenopausal breast cancer. The evidence for higher breast cancer risk after diabetes in pregnancy is conflicting. We compared the incidence of breast and other cancers between pregnant women with and without diabetes. METHODS: This work was a propensity-matched, retrospective cohort study using population-based health-care databases from Ontario, Canada. Those deliveries with gestational diabetes mellitus (GDM) and pregestational diabetes mellitus (pregestational DM) were identified and matched to deliveries without diabetes mellitus (non-DM). Deliveries from each diabetes cohort were matched 1:2 on age, parity, year of delivery, and propensity score to non-DM deliveries. Matched subjects were followed from delivery for incidence of breast cancer as a primary outcome, and other site-specific cancers as secondary outcomes. We performed Cox proportional hazards regression to compare rates of breast cancer between matched groups. RESULTS: Over a median of 8 (interquartile range 4 to 13) years of follow-up, compared with non-DM deliveries, the incidence of breast cancer was significantly lower for GDM but similar for pregestational DM deliveries (hazard ratio [HR] 0.90, 95% confidence interval [CI] 0.82 to 0.98; and HR 0.92, 95% CI 0.80 to 1.07, respectively). GDM was associated with a significantly higher incidence of pancreatic and hepatocellular cancer, and pregestational DM was associated with a higher incidence of thyroid, hepatocellular, and endometrial cancers. CONCLUSIONS: Diabetes in pregnancy does not have a higher short-term risk of subsequent breast cancer, but there may be a higher incidence of other cancers.

Associations of Mid- and Late-Life Severe Hypoglycemic Episodes With Incident Dementia Among Patients With Type 2 Diabetes: A Population-Based Cohort Study.

OBJECTIVE: Severe hypoglycemia is associated with an increased risk of dementia. We examined if the association is consistently present in mid- and late-life hypoglycemia. RESEARCH DESIGN AND METHODS: Using health care data from Population Data BC, we created a base cohort of patients age ≥40 years with incident type 2 diabetes. Exposure was the first occurrence of severe hypoglycemia (hospitalization or physician visit). We assessed exposure versus no exposure in mid- (age 45-64 years) and late-life (age 65-84 years) cohorts. Index date was the later of the 45th birthday (midlife cohort), 65th birthday (late-life cohort), or diabetes diagnosis. Those with hypoglycemia or dementia before the index date were excluded. Patients were followed from index date until dementia diagnosis, death, emigration, or 31 December 2018. Exposure was modeled as time dependent. We adjusted for confounding using propensity score weighting. Dementia risk was estimated using cause-specific hazards models with death as a competing risk. RESULTS: Of 221,683 patients in the midlife cohort, 1,793 experienced their first severe hypoglycemic event. Over a median of 9.14 years, 3,117 dementia outcomes occurred (32 among exposed). Of 223,940 patients in the late-life cohort, 2,466 experienced their first severe hypoglycemic event. Over a median of 6.7 years, 15,997 dementia outcomes occurred (158 among exposed). The rate of dementia was higher for those with (vs. without) hypoglycemia in both the mid- (hazard ratio 2.85; 95% CI 1.72-4.72) and late-life (2.38; 1.83-3.11) cohorts. CONCLUSIONS: Both mid- and late-life hypoglycemia were associated with approximately double the risk of dementia, indicating the need for prevention throughout the life course of those with diabetes.

Hypoglycaemia and the risk of dementia: a population-based cohort study using exposure density sampling.

BACKGROUND: Previous studies have shown hypoglycaemia to be associated with an increased risk of dementia; however, there are several design challenges to consider. The objective of this study is to assess the association between hypoglycaemia and dementia while addressing these challenges using a lag period, exposure density sampling (EDS) and inverse probability of treatment weighting (IPTW). METHODS: This was a population-based cohort using data (1996-2018) from British Columbia, Canada. From a cohort of incident type 2 diabetes patients aged 40-70 years, we created a dynamic sub-cohort of hypoglycaemia-exposed (≥1 episode requiring hospitalization or a physician visit) and unexposed individuals using EDS, in which four unexposed individuals per one exposed were randomly selected into risk sets based on diabetes duration and age. Follow-up was until dementia diagnosis, death, emigration or 31 December 2018. Those diagnosed with dementia within 2 years of follow-up were censored. We adjusted for confounding using IPTW and estimated the hazard ratio (HR, 95% CI) of dementia using weighted conditional cause-specific hazards risk models with death as a competing risk. RESULTS: Among 13 970 patients with incident type 2 diabetes, 2794 experienced hypoglycaemia. There were 329 dementia events over a median (interquartile range: IQR) follow-up of 5.03 (5.7) years. IPTW resulted in well-balanced groups with weighted incidence rates (95% CI) of 4.59 (3.52, 5.98)/1000 person-years among exposed and 3.33 (2.58, 3.88)/1000 person-years among unexposed participants. The risk of dementia was higher among those with hypoglycaemia (HR, 1.83; 95% CI 1.31, 2.57). CONCLUSIONS: After addressing several methodological challenges, we showed that hypoglycaemia contributes to an increased risk of all-cause dementia among patients with type 2 diabetes.

Insulin Use in Type 2 Diabetes and the Risk of Dementia: A Comparative Population-Based Cohort Study.

OBJECTIVE: Evidence of an increased dementia risk with insulin use in type 2 diabetes is weakened by confounding by indication and disease severity. Herein we reassess this association, while accounting for confounding through design and analysis. RESEARCH DESIGN AND METHODS: Using administrative health care data from British Columbia, Canada, we identified patients diagnosed with type 2 diabetes in 1998-2016. To adjust for confounding by diabetes severity through design, we compared new users of insulin to new users of a noninsulin class, both from a restricted cohort of those who previously received two noninsulin antihyperglycemic classes. We further adjusted for confounding using 1) conventional multivariable adjustment and 2) inverse probability of treatment weighting (IPTW) based on the high-dimensional propensity score algorithm. The hazard ratio [HR] (95% CI) of dementia was estimated using cause-specific hazards models with death as a competing risk. RESULTS: The analytical comparative cohort included 7,863 insulin versus 25,230 noninsulin users. At baseline, insulin users were more likely to have worse health indicators. A total of 78 dementia events occurred over a median (interquartile range) follow-up of 3.9 (5.9) years among insulin users, and 179 events occurred over 4.6 (4.4) years among noninsulin users. The HR (95% CI) of dementia for insulin use versus noninsulin use was 1.68 (1.29-2.20) before adjustment and 1.39 (1.05-1.86) after multivariable adjustment, which was further attenuated to 1.14 (0.81-1.60) after IPTW. CONCLUSIONS: Among individuals with type 2 diabetes previously exposed to two noninsulin antihyperglycemic medications, no significant association was observed between insulin use and all-cause dementia.

The Association of Sodium-Glucose Cotransporter 2 Inhibitors With Cardiovascular Outcomes in Anthracycline-Treated Patients With Cancer.

Background: Sodium glucose cotransporter-2 inhibitors (SGLT2is) are hypothesized to reduce the risk of anthracycline-associated cardiotoxicity. Objectives: This study sought to determine the association between SGLT2is and cardiovascular disease (CVD) after anthracycline-containing chemotherapy. Methods: Using administrative data sets, we conducted a population-based cohort study of people >65 years of age with treated diabetes and no prior heart failure (HF) who received anthracyclines between January 1, 2016, and December 31, 2019. After estimating propensity scores for SGLT2i use, the average treatment effects for the treated weights were used to reduce baseline differences between SGLT2i-exposed and -unexposed controls. The outcomes were hospitalization for HF, incident HF diagnoses (in- or out-of-hospital), and documentation of any CVD in future hospitalizations. Death was treated as a competing risk. Cause-specific HRs for each outcome were determined for SGLT2i-treated people relative to unexposed controls. Results: We studied 933 patients (median age 71.0 years, 62.2% female), 99 of whom were SGLT2i treated. During a median follow-up of 1.6 years, there were 31 hospitalizations for HF (0 in the SGLT2i group), 93 new HF diagnoses, and 74 hospitalizations with documented CVD. Relative to controls, SGLT2i exposure was associated with HR of 0 for HF hospitalization (P < 0.001) but no significant difference in incident HF diagnosis (HR: 0.55; 95% CI: 0.23-1.31; P = 0.18) or CVD diagnosis (HR: 0.39; 95% CI: 0.12-1.28; P = 0.12). There was no significant difference in mortality (HR: 0.63; 95% CI: 0.36-1.11; P = 0.11). Conclusions: SGLT2is may reduce the rate of HF hospitalization after anthracycline-containing chemotherapy. This hypothesis warrants further testing in randomized controlled trials.

Association of Different Prescribing Patterns for Oral Corticosteroids With Fracture Preventive Care Among Older Adults in the UK and Ontario.

Importance: Identifying and mitigating modifiable gaps in fracture preventive care for people with relapsing-remitting conditions such as eczema, asthma, and chronic obstructive pulmonary disease who are prescribed high cumulative oral corticosteroid doses may decrease fracture-associated morbidity and mortality. Objective: To estimate the association between different oral corticosteroid prescribing patterns and appropriate fracture preventive care, including treatment with fracture preventive care medications, among older adults with high cumulative oral corticosteroid exposure. Design, Setting, and Participants: This cohort study included 65 195 participants with UK electronic medical record data from the Clinical Practice Research Datalink (January 2, 1998, to January 31, 2020) and 28 674 participants with Ontario, Canada, health administrative data from ICES (April 1, 2002, to September 30, 2020). Participants were adults 66 years or older with eczema, asthma, or chronic obstructive pulmonary disease receiving prescriptions for oral corticosteroids with cumulative prednisolone equivalent doses of 450 mg or higher within 6 months. Data were analyzed October 22, 2020, to September 6, 2022. Exposures: Participants with prescriptions crossing the 450-mg cumulative oral corticosteroid threshold in less than 90 days were classified as having high-intensity prescriptions, and participants crossing the threshold in 90 days or more as having low-intensity prescriptions. Multiple alternative exposure definitions were used in sensitivity analyses. Main Outcomes and Measures: The primary outcome was prescribed fracture preventive care. A secondary outcome was major osteoporotic fracture. Individuals were followed up from the date they crossed the cumulative oral corticosteroid threshold until their outcome or the end of follow-up (up to 1 year after index date). Rates were calculated for fracture preventive care and fractures, and hazard ratios (HRs) were estimated from Cox proportional hazards regression models comparing high- vs low-intensity oral corticosteroid prescriptions. Results: In both the UK cohort of 65 195 participants (mean [IQR] age, 75 [71-81] years; 32 981 [50.6%] male) and the Ontario cohort of 28 674 participants (mean [IQR] age, 73 [69-79] years; 17 071 [59.5%] male), individuals with high-intensity oral corticosteroid prescriptions had substantially higher rates of fracture preventive care than individuals with low-intensity prescriptions (UK: 134 vs 57 per 1000 person-years; crude HR, 2.34; 95% CI, 2.19-2.51, and Ontario: 73 vs 48 per 1000 person-years; crude HR, 1.49; 95% CI, 1.29-1.72). People with high- and low-intensity oral corticosteroid prescriptions had similar rates of major osteoporotic fractures (UK: crude rates, 14 vs 13 per 1000 person-years; crude HR, 1.07; 95% CI, 0.98-1.15 and Ontario: crude rates, 20 vs 23 per 1000 person-years; crude HR, 0.87; 95% CI, 0.79-0.96). Results from sensitivity analyses suggested that reaching a high cumulative oral corticosteroid dose within a shorter time, with fewer prescriptions, or with fewer or shorter gaps between prescriptions, increased fracture preventive care prescribing. Conclusions: The results of this cohort study suggest that older adults prescribed high cumulative oral corticosteroids across multiple prescriptions, or with many or long gaps between prescriptions, may be missing opportunities for fracture preventive care.

Patterns of diabetes testing for older adults without diabetes in Ontario's nursing homes: A population-based study.

BACKGROUND: Asymptomatic diabetes testing may be of limited value for older nursing home residents, but most diabetes guidelines lack upper-age cutoffs for screening cessation. We evaluated patterns of glycated hemoglobin (HbA1c) and serum blood glucose (SBG) testing among older residents without diabetes in Ontario, Canada. METHODS: This population-based retrospective cohort study used provincial health administrative data from ICES to identify older nursing home residents in Ontario without diabetes between January 1, 2015 and December 31, 2018. We examined HbA1c and glucose testing rates overall, by age, sex, and near end-of-life. The number of tests needed to identify one case of diabetes (using HbA1c thresholds of 6.5% and 8.0%) were also calculated. RESULTS: Among 102,923 older nursing home residents (70.3% women; average age 85.6 ± SD 7.7 years), 46.1% of residents received ≥1 HbA1c test over an average follow-up period of 2.15 (± SD 1.49) years, and 18.2% of these tested residents received ≥4 HbA1c tests. The crude HbA1c testing rate was 52.6 tests/100 person-years (95% CI 52.3-52.9). Testing rates among residents aged ≥80 years was 50.7 HbA1c tests/100 person-years (95% CI 50.4-51.0), and 47.8 tests/100 person-years (95% CI 46.5-49.0) among residents near end-of-life. The number of tests to identify a case of diabetes (HbA1c ≥ 6.5%) was 44, while the number of tests to identify a case of actionable diabetes (HbA1c ≥ 8%) was 310. Less than 1% of residents with an HbA1c test met criteria for actionable diabetes. CONCLUSIONS: Nursing home residents without diabetes receive frequent diabetes testing, with high testing rates even in residents over 80 years old and residents near end-of-life. The high number of tests needed to identify a case of actionable diabetes highlights the urgent need to re-evaluate diabetes testing practices in nursing homes.

Lipoprotein(a) Does Not Predict Thrombotic Events and In-Hospital Outcomes in Patients with COVID-19.

The prothrombotic and proinflammatory properties of lipoprotein(a) (Lp(a)) have been hypothesized to play a role in the pathogenesis of severe COVID-19; however, the prognostic impact of Lp(a) on the clinical course of COVID-19 remains controversial. This study aimed to investigate whether Lp(a) may be associated with biomarkers of thrombo-inflammation and the occurrence of thrombotic events or adverse clinical outcomes in patients hospitalized for COVID-19. We consecutively enrolled a cohort of patients hospitalized for COVID-19 and collected blood samples for Lp(a) assessment at hospital admission. A prothrombotic state was evaluated through D-dimer levels, whereas a proinflammatory state was evaluated through C-reactive protein (CRP), procalcitonin, and white blood cell (WBC) levels. Thrombotic events were marked by the diagnosis of deep or superficial vein thrombosis (DVT or SVT), pulmonary embolism (PE), stroke, transient ischemic attack (TIA), acute coronary syndrome (ACS), and critical limb ischemia (CLI). The composite clinical end point of intensive care unit (ICU) admission/in-hospital death was used to evaluate adverse clinical outcomes. Among 564 patients (290 (51%) men, mean age of 74 ± 17 years) the median Lp(a) value at hospital admission was 13 (10-27) mg/dL. During hospitalization, 64 (11%) patients were diagnosed with at least one thrombotic event and 83 (15%) patients met the composite clinical end point. Lp(a), as either a continuous or categorical variable, was not associated with D-dimer, CRP, procalcitonin, and WBC levels (p > 0.05 for all correlation analyses). In addition, Lp(a) was not associated with a risk of thrombotic events (p > 0.05 for multi-adjusted odds ratios) nor with a risk of adverse clinical outcomes (p > 0.05 for multi-adjusted hazard ratios). In conclusion, Lp(a) does not influence biomarkers of plasma thrombotic activity and systemic inflammation nor has any impact on thrombotic events and adverse clinical outcomes in patients hospitalized for COVID-19.

Benefits and Harms of Deprescribing Antihyperglycemics for Adults With Type 2 Diabetes: A Systematic Review.

OBJECTIVES: Contemporary guidelines suggest relaxed glycemic targets in populations with type 2 diabetes mellitus (T2DM) at risk of hypoglycemia, including people with multimorbidity, limited life expectancy or frailty. However, overtreatment remains commonplace. To inform safe deprescribing, a previous systematic review investigated the benefits and harms of deprescribing antihyperglycemics, but identified only limited, very low-quality evidence. We sought to update that review and identify and describe newly published literature on the effects of deprescribing antihyperglycemics in older adults with T2DM. METHODS: We searched MEDLINE, EMBASE and the Cochrane Library (July 2015 to January 2021) for controlled studies published in English addressing the effects of deprescribing vs continuing antihyperglycemics in adults with T2DM. Two independent reviewers performed title, abstract and full-text screening, data extraction and risk-of-bias assessment. Cochrane's risk-of-bias tools, RoB 2 and ROBINS-I, were used. The findings were summarized narratively. GRADE (Grading of Recommendations, Assessment, Development and Evaluations) was used to evaluate the evidence. RESULTS: We identified 4 additional investigations-2 randomized controlled trials and 2 retrospective cohort studies. After deprescribing, 3 studies reported no clinically significant changes in glucose management and 2 studies reported reductions in adverse events (e.g. hypoglycemia, all-cause mortality and nonspine fractures). However, based on GRADE assessment, we found very low certainty of the evidence due to concerns of risk of bias (e.g. unmeasured confounding), imprecision, and indirectness. CONCLUSIONS: Deprescribing antihyperglycemic medications in older adults with T2DM is likely feasible and safe, and benefits may outweigh the harms. However, the evidence indicates very low certainty. Additional deprescribing studies are needed with rigorous methodologies and reporting.