Concurrent Use of Oral Anticoagulants and Sulfonylureas in Individuals With Type 2 Diabetes and Risk of Hypoglycemia: A UK Population-Based Cohort Study

OBJECTIVE: To investigate the association of concurrent use of oral anticoagulants (OACs) and sulfonylureas and the risk of hypoglycemia in individuals with type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS: A retrospective cohort study was conducted between 2001 and 2017 using electronic primary healthcare data from the IQVIA Medical Research Data (IMRD) that incorporates data supplied by The Health Improvement Network (THIN), a propriety database of Cegedim SA. Individuals with T2DM who received OAC prescription and sulfonylureas were included. We compared the risk of hypoglycemia with sulfonylureas and OACs using propensity score matching and Cox regression. RESULTS: 109,040 individuals using warfarin and sulfonylureas and 77,296 using direct oral anticoagulants (DOACs) and sulfonylureas were identified and included. There were 285 hypoglycemia events in the warfarin with sulfonylureas group (incidence rate = 17.8 per 1,000 person-years), while in the sulfonylureas only, 304 hypoglycemia events were observed (incidence rate = 14.4 per 1,000 person-years). There were 14 hypoglycemic events in the DOACs with sulfonylureas group (incidence rates = 14.8 per 1,000 person-years), while in the sulfonylureas alone group, 60 hypoglycemia events were observed (incidence rate =23.7 per 1,000 person-years). Concurrent use of warfarin and sulfonylureas was associated with increased risk of hypoglycemia compared with sulfonylureas alone (HR 1.38; 95% CI 1.10–1.75). However, we found no evidence of an association between concurrent use of DOACs and sulfonylureas and risk of hypoglycemia (HR 0.54; 95% CI, 0.27–1.10) when compared with sulfonylureas only. CONCLUSIONS: We provide real-world evidence of possible drug-drug interactions between warfarin and sulfonylureas. The decision to prescribe warfarin with coexistent sulfonylureas to individuals with T2DM should be carefully evaluated in the context of other risk factors of hypoglycemia, and availability of alternative medications

Hospitalisations related to administration errors of psychotropic drugs: a nationwide retrospective study between 1998 and 2019 in Australia

Objectives: Medication administration error occurs when there is a discrepancy between what the patient received or was planned to receive and what the doctor originally intended. The aim of this study was to examine the trends in hospitalisation related to administration errors of psychotropic drugs in Australia.Materials and Methods: This was a secular trend analysis study that examined the hospitalisation pattern for medication administration errors of psychotropic drugs in Australia between 1998 and 2019. Data on medication administration errors of psychotropic drugs was obtained from The National Hospital Morbidity Database. We analysed the variation in hospitalisation rates using the Pearson chi-square test for independence.Results: Hospitalisation rates related to administration errors of psychotropic drugs increased by 8.3% [from 36.22 (95% CI 35.36—37.08) in 1998 to 39.21 (95% CI 38.44—39.98) in 2019 per 100,000 persons, p < 0.05]. Overnight-stay hospital admission patients accounted for 70.3% of the total number of episodes. Rates of same-day hospitalisation increased by 12.3% [from 10.35 (95% CI 9.90—10.81) in 1998 to 11.63 (95% CI 11.21—12.05) in 2019 per 100,000 persons]. Rates of overnight-stay hospital admission increased by 1.8% [from 25.86 (95% CI 25.13—26.59) in 1998 to 26.34 (95% CI 25.71—26.97) in 2019 per 100,000 persons]. Other and unspecified antidepressants (selective serotonin and norepinephrine reuptake inhibitors) were the most common reason for hospitalisation accounting for 36.6% of the total number of hospitalisation episodes. Females accounted for 111,029 hospitalisation episodes, representing 63.2% of all hospitalisation episodes. The age group 20–39 years accounted for nearly half (48.6%) of the total number of episodes.Conclusion: Psychotropic drug administration error is a regular cause of hospitalization in Australia. Hospitalizations usually required overnight stays. The majority of hospitalizations were in persons aged 20–39 years, which is concerning and warrants further investigation. Future studies should examine the risk factors for hospitalization related to psychiatric drug administration errors

Normal Tissue Complication Probability (NTCP) Prediction Model for Osteoradionecrosis of the Mandible in Patients With Head and Neck Cancer After Radiation Therapy:Large-Scale Observational Cohort

Purpose: Osteoradionecrosis (ORN) of the mandible represents a severe, debilitating complication of radiation therapy (RT) for head and neck cancer (HNC). At present, no normal tissue complication probability (NTCP) models for risk of ORN exist. The aim of this study was to develop a multivariable clinical/dose-based NTCP model for the prediction of ORN any grade (ORNI-IV) and grade IV (ORNIV) after RT (+/- chemotherapy) in patients with HNC.Methods and Materials: Included patients with HNC were treated with (chemo-)RT between 2005 and 2015. Mandible bone radiation dose-volume parameters and clinical variables (ie, age, sex, tumor site, pre-RT dental extractions, chemotherapy history, postoperative RT, and smoking status) were considered as potential predictors. The patient cohort was randomly divided into a training (70%) and independent test (30%) cohort. Bootstrapped forward variable selection was performed in the training cohort to select the predictors for the NTCP models. Final NTCP model(s) were validated on the holdback test subset.Results: Of 1259 included patients with HNC, 13.7% (n = 173 patients) developed any grade ORN (ORNI-IV primary endpoint) and 5% (n = 65) ORNIV (secondary endpoint). All dose and volume parameters of the mandible bone were significantly associated with the development of ORN in univariable models. Multivariable analyses identified D30% and pre-RT dental extraction as independent predictors for both ORNI-IV and ORNIV best-performing NTCP models with an area under the curve (AUC) of 0.78 (AUCvalidation = 0.75 [0.69-0.82]) and 0.81 (AUCvalidation = 0.82 [0.74-0.89]), respectively.Conclusions: This study presented NTCP models based on mandible bone D30% and pre-RT dental extraction that predict ORNI-IV and ORNIV (ie, needing invasive surgical intervention) after HNC RT. Our results suggest that less than 30% of the mandible should receive a dose of 35 Gy or more for an ORNI-IV risk lower than 5%. These NTCP models can improve ORN prevention and management by identifying patients at risk of ORN. (C) 2021 The Author(s). Published by Elsevier Inc.</p

Use of multiple antidiabetic medications in patients with diabetes and its association with hypoglycaemic events

OBJECTIVE: To assess whether the use of multiple antidiabetic medications is associated with an increased risk of hypoglycaemia in patients with type 2 diabetes mellitus. DESIGN: A case-crossover study. SETTING: Cases were enrolled from the National Center for Diabetes, Endocrinology and Genetics in Amman, Jordan. PARTICIPANTS: Patients 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 OUTCOME: History 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. RESULTS: 182 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). CONCLUSION: This 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

In Vitro Anticancer Properties of Novel Bis-Triazoles

Here, we describe the anticancer activity of our novel bis-triazoles MS47 and MS49, developed previously as G-quadruplex stabilizers, focusing specifically upon the human melanoma MDA-MB-435 cell line. At the National Cancer Institute (NCI), USA, bis-triazole MS47 (NCS 778438) was evaluated against a panel of sixty human cancer cell lines, and showed selective, distinct multi-log differential patterns of activity, with GI50 and LC50 values in the sub-micromolar range against human cancer cells. MS47 showed highly selective cytotoxicity towards human melanoma, ovarian, CNS and colon cancer cell lines; in contrast, the leukemia cell lines interestingly showed resistance to MS47 cytotoxic activity. Further studies revealed the potent cell growth inhibiting properties of MS47 and MS49 against the human melanoma MDA-MB-435 cell line, as verified by MTT assays; both ligands were more potent against cancer cells than MRC-5 fetal lung fibroblasts (SI > 9). Melanoma colony formation was significantly suppressed by MS47 and MS49, and time- and dose-dependent apoptosis induction was also observed. Furthermore, MS47 significantly arrested melanoma cells at the G0/G1 cell cycle phase. While the expression levels of Hsp90 protein in melanoma cells were significantly decreased by MS49, corroborating its binding to the G4-DNA promoter of the Hsp90 gene. Both ligands failed to induce senescence in the human melanoma cells after 72 h of treatment, corroborating their weak stabilization of the telomeric G4-DNA

Intensity standardization methods in magnetic resonance imaging of head and neck cancer

BACKGROUND AND PURPOSE: Conventional magnetic resonance imaging (MRI) poses challenges in quantitative analysis because voxel intensity values lack physical meaning. While intensity standardization methods exist, their effects on head and neck MRI have not been investigated. We developed a workflow based on healthy tissue region of interest (ROI) analysis to determine intensity consistency within a patient cohort. Through this workflow, we systematically evaluated intensity standardization methods for MRI of head and neck cancer (HNC) patients.MATERIALS AND METHODS: Two HNC cohorts (30 patients total) were retrospectively analyzed. One cohort was imaged with heterogenous acquisition parameters (HET cohort), whereas the other was imaged with homogenous acquisition parameters (HOM cohort). The standard deviation of cohort-level normalized mean intensity (SD NMI c), a metric of intensity consistency, was calculated across ROIs to determine the effect of five intensity standardization methods on T2-weighted images. For each cohort, a Friedman test followed by a post-hoc Bonferroni-corrected Wilcoxon signed-rank test was conducted to compare SD NMI c among methods. RESULTS: Consistency (SD NMI c across ROIs) between unstandardized images was substantially more impaired in the HET cohort (0.29 ± 0.08) than in the HOM cohort (0.15 ± 0.03). Consequently, corrected p-values for intensity standardization methods with lower SD NMI c compared to unstandardized images were significant in the HET cohort (p &lt; 0.05) but not significant in the HOM cohort (p &gt; 0.05). In both cohorts, differences between methods were often minimal and nonsignificant. CONCLUSIONS: Our findings stress the importance of intensity standardization, either through the utilization of uniform acquisition parameters or specific intensity standardization methods, and the need for testing intensity consistency before performing quantitative analysis of HNC MRI.</p

Mental illness stigma as a moderator in the relationship between religiosity and help-seeking attitudes among Muslims from 16 Arab countries

Background: Determining the potential barriers responsible for delaying access to care, and elucidating pathways to early intervention should be a priority, especially in Arab countries where mental health resources are limited. To the best of our knowledge, no previous studies have examined the relationship between religiosity, stigma and help-seeking in an Arab Muslim cultural background. Hence, we propose in the present study to test the moderating role of stigma toward mental illness in the relationship between religiosity and help-seeking attitudes among Muslim community people living in different Arab countries. Method: The current survey is part of a large-scale multinational collaborative project (StIgma of Mental Problems in Arab CounTries [The IMPACT Project]). We carried-out a web-based cross-sectional, and multi-country study between June and November 2021. The final sample comprised 9782 Arab Muslim participants (mean age 29.67 ± 10.80 years, 77.1% females). Results: Bivariate analyses showed that less stigmatizing attitudes toward mental illness and higher religiosity levels were significantly associated with more favorable help-seeking attitudes. Moderation analyses revealed that the interaction religiosity by mental illness stigma was significantly associated with help-seeking attitudes (Beta =.005; p \u3c.001); at low and moderate levels of stigma, higher religiosity was significantly associated with more favorable help-seeking attitudes. Conclusion: Our findings preliminarily suggest that mental illness stigma is a modifiable individual factor that seems to strengthen the direct positive effect of religiosity on help-seeking attitudes. This provides potential insights on possible anti-stigma interventions that might help overcome reluctance to counseling in highly religious Arab Muslim communities

Perspectives, practices, and challenges of online teaching during COVID-19 pandemic: A multinational survey

The result of the movement restrictions during the COVID-19 pandemic was an impromptu and abrupt switch from in-person to online teaching. Most focus has been on the perception and experience of students during the process. The aim of this international survey is to assess staffs' perspectives and challenges of online teaching during the COVID-19 lockdown. Cross-sectional research using a validated online survey was carried out in seven countries (Brazil, Saudi Arabia, Jordan, Indonesia, India, the United Kingdom, and Egypt) between the months of December 2021 and August 2022, to explore the status of online teaching among faculty members during the COVID-19 pandemic. Variables and response are presented as percentages while logistic regression was used to assess the factors that predict levels of satisfaction and the challenges associated with online instruction. A total of 721 response were received from mainly male (53%) staffs. Most respondents are from Brazil (59%), hold a Doctorate degree (70%) and have over 10 years of working experience (62%). Although, 67% and 79% have relevant tools and received training for online teaching respectively, 44% report that online teaching required more preparation time than face-to-face. Although 41% of respondents were uncertain about the outcome of online teaching, 49% were satisfied with the process. Also, poor internet bandwidth (51%), inability to track students' engagement (18%) and Lack of technical skills (11.5%) were the three main observed limitations. Having little or no prior experience of online teaching before the COVID-19 pandemic [OR, 1.58 (95% CI, 1.35–1.85)], and not supporting the move to online teaching mode [OR, 0.56 (95% CI,0.48–0.64)] were two main factors independently linked with dissatisfaction with online teaching. While staffs who support the move to online teaching were twice likely to report no barriers [OR, 2.15 (95% CI, 1.61–2.86)]. Although, relevant tools and training were provided to support the move to online teaching during COVID-19 lockdown, barriers such as poor internet bandwidth, inability to track students’ engagement and lack of technical skills were main limitations observed internationally by teaching staffs. Addressing these barriers should be the focus of higher education institution in preparation for future disruptions to traditional teaching modes

Cross-cultural comparison of mental illness stigma and help-seeking attitudes: a multinational population-based study from 16 Arab countries and 10,036 individuals

BackgroundThere is evidence that culture deeply affects beliefs about mental illnesses\u27 causes, treatment, and help-seeking. We aimed to explore and compare knowledge, attitudes toward mental illness and help-seeking, causal attributions, and help-seeking recommendations for mental illnesses across various Arab countries and investigate factors related to attitudes toward help-seeking.MethodsWe carried out a multinational cross-sectional study using online self-administered surveys in the Arabic language from June to November 2021 across 16 Arab countries among participants from the general public.ResultsMore than one in four individuals exhibited stigmatizing attitudes towards mental illness (26.5%), had poor knowledge (31.7%), and hold negative attitudes toward help-seeking (28.0%). ANOVA tests revealed a significant difference between countries regarding attitudes (F = 194.8, p \u3c .001), knowledge (F = 88.7, p \u3c .001), and help-seeking attitudes (F = 32.4, p \u3c .001). Three multivariate regression analysis models were performed for overall sample, as well as Palestinian and Sudanese samples that displayed the lowest and highest ATSPPH-SF scores, respectively. In the overall sample, being female, older, having higher knowledge and more positive attitudes toward mental illness, and endorsing biomedical and psychosocial causations were associated with more favorable help-seeking attitudes; whereas having a family psychiatric history and endorsing religious/supernatural causations were associated with more negative help-seeking attitudes. The same results have been found in the Palestinian sample, while only stigma dimensions helped predict help-seeking attitudes in Sudanese participants.ConclusionInterventions aiming at improving help-seeking attitudes and behaviors and promoting early access to care need to be culturally tailored, and congruent with public beliefs about mental illnesses and their causations

Concurrent Use of Oral Anticoagulants and Sulfonylureas in Individuals With Type 2 Diabetes and Risk of Hypoglycemia: A UK Population-Based Cohort Study

ObjectiveTo investigate the association of concurrent use of oral anticoagulants (OACs) and sulfonylureas and the risk of hypoglycemia in individuals with type 2 diabetes mellitus (T2DM).Research Design and MethodsA retrospective cohort study was conducted between 2001 and 2017 using electronic primary healthcare data from the IQVIA Medical Research Data (IMRD) that incorporates data supplied by The Health Improvement Network (THIN), a propriety database of Cegedim SA. Individuals with T2DM who received OAC prescription and sulfonylureas were included. We compared the risk of hypoglycemia with sulfonylureas and OACs using propensity score matching and Cox regression.Results109,040 individuals using warfarin and sulfonylureas and 77,296 using direct oral anticoagulants (DOACs) and sulfonylureas were identified and included. There were 285 hypoglycemia events in the warfarin with sulfonylureas group (incidence rate = 17.8 per 1,000 person-years), while in the sulfonylureas only, 304 hypoglycemia events were observed (incidence rate = 14.4 per 1,000 person-years). There were 14 hypoglycemic events in the DOACs with sulfonylureas group (incidence rates = 14.8 per 1,000 person-years), while in the sulfonylureas alone group, 60 hypoglycemia events were observed (incidence rate =23.7 per 1,000 person-years). Concurrent use of warfarin and sulfonylureas was associated with increased risk of hypoglycemia compared with sulfonylureas alone (HR 1.38; 95% CI 1.10–1.75). However, we found no evidence of an association between concurrent use of DOACs and sulfonylureas and risk of hypoglycemia (HR 0.54; 95% CI, 0.27–1.10) when compared with sulfonylureas only.ConclusionsWe provide real-world evidence of possible drug-drug interactions between warfarin and sulfonylureas. The decision to prescribe warfarin with coexistent sulfonylureas to individuals with T2DM should be carefully evaluated in the context of other risk factors of hypoglycemia, and availability of alternative medications