scholarly journals Use of multiple antidiabetic medications in patients with diabetes and its association with hypoglycaemic events: a case-crossover study in Jordan

BMJ Open ◽  
2018 ◽  
Vol 8 (11) ◽  
pp. e024909 ◽  
Author(s):  
Abdallah Y Naser ◽  
Ian Chi Kei Wong ◽  
Cate Whittlesea ◽  
Maedeh Y Beykloo ◽  
Kenneth K C Man ◽  
...  

ObjectiveTo assess whether the use of multiple antidiabetic medications is associated with an increased risk of hypoglycaemia in patients with type 2 diabetes mellitus.DesignA case-crossover study.SettingCases were enrolled from the National Center for Diabetes, Endocrinology and Genetics in Amman, Jordan.ParticipantsPatients were those with diabetes mellitus and reported incident of a hypoglycaemic event in their medical records during the period January 2007 to July 2017. Patients with multiple antidiabetic medications were those with at least two antidiabetic medications.Primary outcomeHistory of antidiabetic medication use was extracted from the pharmacy records. The use of multiple antidiabetic medications during the risk window (before hypoglycaemia) was compared with a control window(s) (earlier time) of the same length after a washout period. Conditional logistic regression was applied to evaluate the OR of hypoglycaemia between the treatment groups. A secondary analysis was performed in patients with a blood glucose measurement of ≤70 mg/dL.Results182 patients (106 females, 58.2%) were included in the study with an average age of 59.9 years (SD=9.9). The patients’ average body mass index was 31.7 kg/m2 (SD=6.2). Compared with monotherapy, the OR of hypoglycaemic events for patients with multiple antidiabetic medications was 5.00 (95% CI 1.10 to 22.82). The OR was 6.00 (95% CI 0.72 to 49.84) for the secondary analysis patient group (n=94). Ten-fold increased risk was found in patients (n=155) with insulin and sulfonylurea-based combination therapy (OR 10.00;95% CI 1.28 to 78.12).ConclusionThis study shows that the use of multiple antidiabetic medications appears to increase the risk of hypoglycaemic events. Patients and healthcare professionals should be extra vigilant when patients are on multiple antidiabetic medications therapy, especially the combination of sulfonylurea and insulin.

PLoS Medicine ◽  
2021 ◽  
Vol 18 (10) ◽  
pp. e1003759
Author(s):  
Dan Lewer ◽  
Brian Eastwood ◽  
Martin White ◽  
Thomas D. Brothers ◽  
Martin McCusker ◽  
...  

Background Hospital patients who use illicit opioids such as heroin may use drugs during an admission or leave the hospital in order to use drugs. There have been reports of patients found dead from drug poisoning on the hospital premises or shortly after leaving the hospital. This study examines whether hospital admission and discharge are associated with increased risk of opioid-related death. Methods and findings We conducted a case-crossover study of opioid-related deaths in England. Our study included 13,609 deaths between January 1, 2010 and December 31, 2019 among individuals aged 18 to 64. For each death, we sampled 5 control days from the period 730 to 28 days before death. We used data from the national Hospital Episode Statistics database to determine the time proximity of deaths and control days to hospital admissions. We estimated the association between hospital admission and opioid-related death using conditional logistic regression, with a reference category of time neither admitted to the hospital nor within 14 days of discharge. A total of 236/13,609 deaths (1.7%) occurred following drug use while admitted to the hospital. The risk during hospital admissions was similar or lower than periods neither admitted to the hospital nor recently discharged, with odds ratios 1.03 (95% CI 0.87 to 1.21; p = 0.75) for the first 14 days of an admission and 0.41 (95% CI 0.30 to 0.56; p < 0.001) for days 15 onwards. 1,088/13,609 deaths (8.0%) occurred in the 14 days after discharge. The risk of opioid-related death increased in this period, with odds ratios of 4.39 (95% CI 3.75 to 5.14; p < 0.001) on days 1 to 2 after discharge and 2.09 (95% CI 1.92 to 2.28; p < 0.001) on days 3 to 14. 11,629/13,609 deaths (85.5%) did not occur close to a hospital admission, and the remaining 656/13,609 deaths (4.8%) occurred in hospital following admission due to drug poisoning. Risk was greater for patients discharged from psychiatric admissions, those who left the hospital against medical advice, and those leaving the hospital after admissions of 7 days or more. The main limitation of the method is that it does not control for time-varying health or drug use within individuals; therefore, hospital admissions coinciding with high-risk periods may in part explain the results. Conclusions Discharge from the hospital is associated with an acute increase in the risk of opioid-related death, and 1 in 14 opioid-related deaths in England happens in the 2 weeks after the hospital discharge. This supports interventions that prevent early discharge and improve linkage with community drug treatment and harm reduction services.


TH Open ◽  
2019 ◽  
Vol 03 (01) ◽  
pp. e50-e57
Author(s):  
Vânia Morelli ◽  
Joakim Sejrup ◽  
Birgit Småbrekke ◽  
Ludvig Rinde ◽  
Gro Grimnes ◽  
...  

AbstractStroke is associated with a short-term increased risk of subsequent venous thromboembolism (VTE). It is unclear to what extent this association is mediated by stroke-related complications that are potential triggers for VTE, such as immobilization and infection. We aimed to investigate the role of acute stroke as a trigger for incident VTE while taking other concomitant VTE triggers into account. We conducted a population-based case-crossover study with 707 VTE patients. Triggers were registered during the 90 days before a VTE event (hazard period) and in four preceding 90-day control periods. Conditional logistic regression was used to estimate odds ratios with 95% confidence intervals (CIs) for VTE according to triggers. Stroke was registered in 30 of the 707 (4.2%) hazard periods and in 6 of the 2,828 (0.2%) control periods, resulting in a high risk of VTE, with odds ratios of 20.0 (95% CI: 8.3–48.1). After adjustments for immobilization and infection, odds ratios for VTE conferred by stroke were attenuated to 6.0 (95% CI: 1.6–22.1), and further to 4.0 (95% CI: 1.1–14.2) when other triggers (major surgery, red blood cell transfusion, trauma, and central venous catheter) were added to the regression model. A mediation analysis revealed that 67.8% of the total effect of stroke on VTE risk could be mediated through immobilization and infection. Analyses restricted to ischemic stroke yielded similar results. In conclusion, acute stroke was a trigger for VTE, and the association between stroke and VTE risk appeared to be largely mediated by immobilization and infection.


Cephalalgia ◽  
2014 ◽  
Vol 35 (3) ◽  
pp. 203-210 ◽  
Author(s):  
Jen-Feng Liang ◽  
Yung-Tai Chen ◽  
Jong-Ling Fuh ◽  
Szu-Yuan Li ◽  
Tzeng-Ji Chen ◽  
...  

Background Headaches resulting from proton pump inhibitor (PPI) use could cause discontinuation of PPI in as many as 40% of patients who experience such headaches. Previous studies focusing on acute headache risk from PPI use are rare and limited to clinical trials of a single PPI. Objectives To investigate the association between PPI use and headache with a nationwide population-based case-crossover study. Methods Records containing the first diagnosis of any headache, including migraine and tension-type headaches, were retrieved from Taiwan National Health Insurance Database (1998–2010). We compared the rates of PPI use for cases and controls during time windows of 7, 14, and 28 days. The adjusted self-matched odds ratios (ORs) and 95% confidence intervals (CIs) from a conditional logistic regression model were used to determine the association between PPI use and headache. Results Overall, 314,210 patients with an initial diagnosis of any headache during the study period were enrolled. The adjusted ORs for headache risk after PPI exposure were calculated for three time periods (within 7 days = 1.41, p = 0.002, 95% CI 1.14–1.74; within 14 days = 1.36, p < 0.001, 95% CI 1.16–1.59; within 28 days = 1.20, p = 0.002, 95% CI 1.07–1.35). Subgroup analyses showed female patients had an increased risk of headache. Among PPIs, lansoprazole and esomeprazole had the highest risks of headache incidence, which were similar to that of nitrates. Conclusion PPI usage is associated with an increased risk for acute headache. Female patients and use of lansoprazole or esomeprazole present the greatest risks of headache.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lamiae Grimaldi-Bensouda ◽  
Bernard Begaud ◽  
Jacques Benichou ◽  
Clementine Nordon ◽  
Olivia Dialla ◽  
...  

AbstractPharmacovigilance reports of cerebral and cardiovascular events in those who use decongestants have triggered alerts related to their use. We aimed to assess the risk of stroke and myocardial infarction (MI) associated with the use of decongestants. We conducted a nested case-crossover study of patients with incident stroke and MI identified in France between 2013 and 2016 in two systematic disease registries. Decongestant use in the three weeks preceding the event was assessed using a structured telephone interview. Conditional logistic multivariable models were used to estimate the odds of incident MI and stroke, also accounting for transient risk factors and comparing week 1 (index at-risk time window, immediately preceding the event) to week 3 (reference). Time-invariant risk factors were controlled by design. In total, 1394 patients with MI and 1403 patients with stroke, mainly 70 years old or younger, were interviewed, including 3.2% who used decongestants during the three weeks prior to the event (1.0% definite exposure in the index at-risk time window, 1.1% in the referent time window; adjusted odds ratio (aOR), 0.78; 95%CI, 0.43–1.42). Secondary analysis yielded similar results for individual events (MI/stroke). We observed no increased risk of MI or stroke for patients 70 years of age and younger without previous MI or stroke who used decongestants.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 808.1-809
Author(s):  
F. Roemer ◽  
J. Collins ◽  
T. Neogi ◽  
M. Crema ◽  
A. Guermazi

Background:Imaging plays an important role in determining structural disease severity and potential suitability of patients recruited to disease-modifying osteoarthritis drug (DMOAD) trials. It has been suggested that there may be three main structural phenotypes in OA, i.e., inflammation, meniscus/cartilage and subchondral bone. These may progress differently and may represent distinct tissue targets for DMOAD approaches.Objectives:To stratify the Foundation for National Institutes of Health Osteoarthritis Biomarkers Consortium (FNIH) cohort, a well-defined subsample of the larger Osteoarthritis Initiative (OAI) study, into distinct structural phenotypes based on semiquantitative MRI assessment and to determine their risk for progression over 48 months.Methods:The FNIH was designed as a case-control study with knees showing either 1) radiographic and pain progression (i.e., “composite” cases), 2) radiographic progression only (“JSL”), 3) pain progression only, and 4) neither radiographic nor pain progression. MRI of both knees was performed on 3 T systems at the four OAI clinical sites. Two musculoskeletal radiologists read the baseline MRIs according to the MOAKS scoring system. Knees were stratified into subchondral bone, meniscus/cartilage and inflammatory phenotypes1. A secondary, less stringent definition for inflammatory and meniscus/cartilage phenotype was used for sensitivity analyses. The relation of each phenotype to risk of being in the JSL or composite case group compared to those not having that phenotype was determined using conditional logistic regression. Only KL2 and 3 and those without root tears were included.Results:485 knees were included. 362 (75%) did not have any phenotype, while 95 (20%) had the bone phenotype, 22 (5%) the cartilage/meniscus phenotype and 19 (4%) the inflammatory phenotype. The bone phenotype was associated with a higher risk of the JSL and composite outcome (OR 1.81;[95%CI 1.14,2.85] and 1.65; 95%CI [1.04,2.61]) while the inflammatory (OR 0.96 [95%CI 0.38,2.42] and 1.25; 95%CI [0.48,3.25]) and the meniscus/cartilage phenotypes were not (OR 1.30 95%CI [0.55,3.07] and 0.99; 95%CI [0.40,2,49]).In sensitivity analyses, the bone phenotype and having two phenotypes (vs. none) were both associated with increased risk of experiencing the composite outcome (bone: OR 1.65; 95% CI 1.04, 2.61; 2 phenotypes: OR 1.87; 95% CI 1.11, 3.16.Conclusion:The bone phenotype was associated with increased risk of having both radiographic and pain progression together, or radiographic progression alone, whereas the inflammatory phenotype or meniscus/cartilage phenotype each individually were not associated with either outcome. Phenotypic stratification appears to provide insights into risk for structural or composite structure plus pain progression, and therefore may be useful to consider when selecting patients for inclusion in clinical trials.References:[1]Roemer FW, Collins J, Kwoh CK, et al. MRI-based screening for structural definition of eligibility in clinical DMOAD trials: Rapid OsteoArthritis MRI Eligibility Score (ROAMES). Osteoarthritis Cartilage 2020;28(1):71-81Disclosure of Interests:Frank Roemer: None declared, Jamie Collins Consultant of: Boston Imaging Core Lab (BICL), LLC., Tuhina Neogi Grant/research support from: Pfizer/Lilly, Consultant of: Pfizer/Lilly, EMD-Merck Serono, Novartis, Michel Crema: None declared, Ali Guermazi Consultant of: AventisGalapagos, Pfizer, Roche, AstraZeneca, Merck Serono, and TissuGene


2021 ◽  
pp. 1-10
Author(s):  
Takeshi Hasegawa ◽  
Junhui Zhao ◽  
Brian Bieber ◽  
Jarcy Zee ◽  
Ronald L. Pisoni ◽  
...  

<b><i>Introduction:</i></b> Dipeptidyl peptidase-4 (DPP-4) has been hypothesized to improve responsiveness to erythropoiesis-stimulating agent (ESA). We aimed to describe the trend in DPP-4 inhibitor prescription patterns and assess the association between DPP-4 inhibitor prescription and ESA hyporesponsiveness (eHypo) in Japanese hemodialysis (HD) patients with diabetes mellitus (DM). <b><i>Methods:</i></b> We analyzed data from the Japan Dialysis Outcomes and Practice Patterns Study phase 4–6 (2009–2017) on patients with DM who underwent HD thrice per week for at least 4 months. The primary exposure of interest was having a DPP-4 inhibitor prescription. The primary analysis outcomes were a binary indicator of eHypo (mean hemoglobin &#x3c;10 and mean ESA dose &#x3e;6,000 units/week over 4 months) and the natural log-transformed ESA resistance index (ERI). We used conditional logistic regression to compare within-patient changes in eHypo before and after initial DPP-4 inhibitor prescription. We used linear generalized estimating equation models to compare continuous ERI outcomes while accounting for within-patient repeated measurements with an exchangeable correlation structure. <b><i>Results:</i></b> There was a monotonic increase in DPP-4 inhibitor prescription according to study year up to 20% in 2017. Moreover, 12.8% of patients with a DPP-4 inhibitor prescription were ESA hyporesponsive before the initial DPP-4 inhibitor prescription. After DPP-4 inhibitor prescription, the odds of eHypo and mean log-ERI remained unchanged in the whole cohort of our study. The interaction analysis of DPP-4 inhibitor and sideropenia showed that DPP-4 inhibitors attenuated eHypo in the patients without iron deficiency. <b><i>Conclusion:</i></b> Our findings indicate a recent increase in DPP-4 inhibitor prescription among Japanese HD patients with DM. DPP-4 inhibitors could improve ERI in patients undergoing HD without iron deficiency.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Kiyoshi Kubota ◽  
Thu-Lan Kelly ◽  
Tsugumichi Sato ◽  
Nicole Pratt ◽  
Elizabeth Roughead ◽  
...  

Abstract Background Case-crossover studies have been widely used in various fields including pharmacoepidemiology. Vines and Farrington indicated in 2001 that when within-subject exposure dependency exists, conditional logistic regression can be biased. However, this bias has not been well studied. Methods We have extended findings by Vines and Farrington to develop a weighting method for the case-crossover study which removes bias from within-subject exposure dependency. Our method calculates the exposure probability at the case period in the case-crossover study which is used to weight the likelihood formulae presented by Greenland in 1999. We simulated data for the population with a disease where most patients receive a cyclic treatment pattern with within-subject exposure dependency but no time trends while some patients stop and start treatment. Finally, the method was applied to real-world data from Japan to study the association between celecoxib and peripheral edema and to study the association between selective serotonin reuptake inhibitor (SSRI) and hip fracture in Australia. Results When the simulated rate ratio of the outcome was 4.0 in a case-crossover study with no time-varying confounder, the proposed weighting method and the Mantel-Haenszel odds ratio reproduced the true rate ratio. When a time-varying confounder existed, the Mantel-Haenszel method was biased but the weighting method was not. When more than one control period was used, standard conditional logistic regression was biased either with or without time-varying confounding and the bias increased (up to 8.7) when the study period was extended. In real-world analysis with a binary exposure variable in Japan and Australia, the point estimate of the odds ratio (around 2.5 for the association between celecoxib and peripheral edema and around 1.6 between SSRI and hip fracture) by our weighting method was equal to the Mantel-Haenszel odds ratio and stable compared with standard conditional logistic regression. Conclusion Case-crossover studies may be biased from within-subject exposure dependency, even without exposure time trends. This bias can be identified by comparing the odds ratio by the Mantel-Haenszel method and that by standard conditional logistic regression. We recommend using our proposed method which removes bias from within-subject exposure dependency and can account for time-varying confounders.


2019 ◽  
pp. S107-S120 ◽  
Author(s):  
J. JACKULIAK ◽  
M. KUŽMA ◽  
J. PAYER

Patients with diabetes mellitus are at an increased risk of bone fractures. Several groups of effective antidiabetic drugs are available, which are very often given in combination. The effects of these medications on bone metabolism and fracture risk must not be neglected. Commonly used antidiabetic drugs might have a positive, neutral or negative impact on skeletal health. Increased risk of fracture has been identified with use of thiazolidinediones, most definitively in women. Also treatment with sulfonylureas can have adverse effects on bone. One consequence of these findings has been greater attention to fracture outcomes in trails of new diabetes medication (incretins and SGLT-2 inhibitors). The effect of insulin on bone is discussed and the risk of fractures in patients using insulin seems to be unrelated to insulin as itself. The aim of the review is to summarize effects of antidiabetic treatment on bone – bone mineral density, fractures and bone turnover markers. The authors also try to recommend a strategy how to treat patients with diabetes mellitus regarding the risk of osteoporotic fractures. In this review the problem of how to treat osteoporosis in patient with diabetes is also discussed.


Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Gautam R Shroff ◽  
Craig A Solid ◽  
Charles A Herzog

Background: Patients with diabetes mellitus (DM) and non valvular atrial fibrillation (AF) are at increased risk of ischemic stroke; but evidence regarding ischemic stroke and warfarin use in the literature is limited. We evaluated temporal trends in ischemic stroke and warfarin use among the US Medicare population with and without DM. Methods: One-year cohorts of patients with Medicare as primary payer, 1992-2010, were created using the Medicare 5% sample. ICD-9-CM codes were used to identify AF, ischemic and hemorrhagic stroke and comorbidities; ≤3 consecutive prothrombin-time claims were used to identify warfarin use. Results: Demographic characteristics between 1992 (n=40255) and 2010 (n=80314) respectively were (proportions): age 65-74 years (37%, 32%); age ≤ 85 years (20%, 25%); white (94%, 93%); hypertension (46%, 80%); DM (20%, 32%), chronic kidney disease (5%, 18%). Ischemic stroke rates among Medicare AF patients with DM decreased by 71% (1992, 2010) from 65 to 19 /1000 patient-years; warfarin utilization increased from 28% to 62% respectively (Figure 1A). Among Medicare AF patients without DM, ischemic stroke rates decreased by 68% from 44 to 14/ 1000 patient-years; warfarin use increased 26% to 59% respectively (Figure 1B). About 38% Medicare AF pts with DM did not receive anticoagulation in 2010. Conclusion: Medicare patients with and without DM had a similar reduction in ischemic stroke rates; and similar increase in warfarin utilization over the study period. A significant proportion of Medicare pts with DM did not receive anticoagulation with warfarin for AF in 2010; this population deserves future attention.


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