Real-world evidence on sodium-glucose cotransporter-2 inhibitor use and risk of Fournier’s gangrene

BackgroundSodium-glucose cotransporter-2 inhibitors (SGLT2i) have been associated with increased occurrence of Fournier’s gangrene (FG), a rare but serious form of necrotizing fasciitis, leading to a warning from the Food and Drug Administration. Real-world evidence on FG is needed to validate this warning.MethodsWe used data from IBM MarketScan (2013–2017) to compare the incidence of FG among adult patients who initiated either SGLT2i, a dipeptidyl peptidase-4 inhibitor (DPP4i), or any non-SGLT2i antihyperglycemic medication. FG was defined using inpatient International Classification of Diseases, Ninth Edition and Tenth Edition diagnosis codes 608.83 and N49.3, respectively, combined with procedure codes for debridement, surgery, or systemic antibiotics. We estimated crude incidence rates (IRs) using Poisson regression, and crude and adjusted HRs (aHR) and 95% CIs using standardized mortality ratio-weighted Cox proportional hazards models. Sensitivity analyses examined the impact of alternative outcome definitions.ResultsWe identified 211 671 initiators of SGLT2i (n=93 197) and DPP4i (n=118 474), and 305 329 initiators of SGLT2i (n=32 868) and non-SGLT2i (n=272 461). Crude FG IR ranged from 3.2 to 3.8 cases per 100 000 person-years during a median follow-up of 0.51–0.58 years. Compared with DPP4i, SGLT2i initiation was not associated with increased risk of FG for any outcome definition, with aHR estimates ranging from 0.25 (0.04–1.74) to 1.14 (0.86–1.51). In the non-SGLT2i comparison, we observed an increased risk of FG for SGLT2i initiators when using FG diagnosis codes alone, using all diagnosis settings (aHR 1.80; 0.53–6.11) and inpatient diagnoses only (aHR 4.58; 0.99–21.21).ConclusionsNo evidence of increased risk of FG associated with SGLT2i was observed compared with DPP4i, arguably the most relevant clinical comparison. However, uncertainty remains based on potentially higher risk in the broader comparison with all non-SGLT2i antihyperglycemic agents and the rarity of FG.Trial registration numberEUPAS Register Number 30018.

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1607-P: Real-World Evidence of the Impact of Obesity on Residual Teeth in the Japanese Population

Diabetes ◽

10.2337/db20-1607-p ◽

2020 ◽

Vol 69 (Supplement 1) ◽

pp. 1607-P

Author(s):

MAYU HAYASHI ◽

KATSUTARO MORINO ◽

KAYO HARADA ◽

MIKI ISHIKAWA ◽

ITSUKO MIYAZAWA ◽

...

Keyword(s):

Real World ◽

Japanese Population ◽

Real World Evidence ◽

The Impact

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Body mass index and risk of all-cause mortality in normotensive and hypertensive adults: The Rural Chinese Cohort Study

Public Health Nutrition ◽

10.1017/s1368980021001592 ◽

2021 ◽

pp. 1-25

Author(s):

Qionggui Zhou ◽

Xuejiao Liu ◽

Yang Zhao ◽

Pei Qin ◽

Yongcheng Ren ◽

...

Keyword(s):

Cohort Study ◽

Population Based ◽

Normal Weight ◽

Sensitivity Analyses ◽

Hypertension Status ◽

Moderation Effect ◽

Increased Risk ◽

All Cause Mortality ◽

Chinese Cohort ◽

The Impact

Abstract Objective: The impact of baseline hypertension status on the BMI–mortality association is still unclear. We aimed to examine the moderation effect of hypertension on the BMI–mortality association using a rural Chinese cohort. Design: In this cohort study, we investigated the incident of mortality according to different BMI categories by hypertension status. Setting: Longitudinal population-based cohort Participants: 17,262 adults ≥18 years were recruited from July to August of 2013 and July to August of 2014 from a rural area in China. Results: During a median 6-year follow-up, we recorded 1109 deaths (610 with and 499 without hypertension). In adjusted models, as compared with BMI 22-24 kg/m2, with BMI ≤18, 18-20, 20-22, 24-26, 26-28, 28-30 and >30 kg/m2, the HRs (95% CI) for mortality in normotensive participants were 1.92 (1.23-3.00), 1.44 (1.01-2.05), 1.14 (0.82-1.58), 0.96 (0.70-1.31), 0.96 (0.65-1.43), 1.32 (0.81-2.14), and 1.32 (0.74-2.35) respectively, and in hypertensive participants were 1.85 (1.08-3.17), 1.67 (1.17-2.39), 1.29 (0.95-1.75), 1.20 (0.91-1.58), 1.10 (0.83-1.46), 1.10 (0.80-1.52), and 0.61 (0.40-0.94) respectively. The risk of mortality was lower in individuals with hypertension with overweight or obesity versus normal weight, especially in older hypertensives (≥60 years old). Sensitivity analyses gave consistent results for both normotensive and hypertensive participants. Conclusions: Low BMI was significantly associated with increased risk of all-cause mortality regardless of hypertension status in rural Chinese adults, but high BMI decreased the mortality risk among individuals with hypertension, especially in older hypertensives.

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Gastrostomy Tubes Placed in Children With Neurologic Impairment: Associated Morbidity and Mortality

Journal of Child Neurology ◽

10.1177/08830738211000179 ◽

2021 ◽

pp. 088307382110001

Author(s):

Jody L. Lin ◽

Joseph Rigdon ◽

Keith Van Haren ◽

MyMy Buu ◽

Olga Saynina ◽

...

Keyword(s):

Severe Pneumonia ◽

Sensitivity Analyses ◽

Tube Placement ◽

Composite Outcome ◽

Eligibility Criteria ◽

Risk Of Death ◽

Cox Proportional Hazard ◽

Neurologic Impairment ◽

Increased Risk ◽

The Impact

Background: Gastrostomy tube (G-tube) placement for children with neurologic impairment with dysphagia has been suggested for pneumonia prevention. However, prior studies demonstrated an association between G-tube placement and increased risk of pneumonia. We evaluate the association between timing of G-tube placement and death or severe pneumonia in children with neurologic impairment. Methods: We included all children enrolled in California Children’s Services between July 1, 2009, and June 30, 2014, with neurologic impairment and 1 pneumonia hospitalization. Prior to analysis, children with new G-tubes and those without were 1:2 propensity score matched on sociodemographics, medical complexity, and severity of index hospitalization. We used a time-varying Cox proportional hazard model for subsequent death or composite outcome of death or severe pneumonia to compare those with new G-tubes vs those without, adjusting for covariates described above. Results: A total of 2490 children met eligibility criteria, of whom 219 (9%) died and 789 (32%) had severe pneumonia. Compared to children without G-tubes, children with new G-tubes had decreased risk of death (hazard ratio [HR] 0.47, 95% confidence interval [CI] 0.39-0.55) but increased risk of the composite outcome (HR 1.21, CI 1.14-1.27). Sensitivity analyses using varied time criteria for definitions of G-tube and outcome found that more recent G-tube placement had greater associated risk reduction for death but increased risk of severe pneumonia. Conclusion: Recent G-tube placement is associated with reduced risk of death but increased risk of severe pneumonia. Decisions to place G-tubes for pulmonary indications in children with neurologic impairment should weigh the impact of severe pneumonia on quality of life.

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The impact of anti-CGRP monoclonal antibodies in resistant migraine patients: a real-world evidence observational study

Journal of Neurology ◽

10.1007/s00415-021-10523-8 ◽

2021 ◽

Author(s):

Marta Torres-Ferrús ◽

Victor J. Gallardo ◽

Alicia Alpuente ◽

Edoardo Caronna ◽

Eulalia Gine-Cipres ◽

...

Keyword(s):

Monoclonal Antibodies ◽

Observational Study ◽

Real World ◽

Real World Evidence ◽

The Impact

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Pharmacovigilance assessment of the association between Fournier’s gangrene and other severe genital adverse events with SGLT-2 inhibitors

BMJ Open Diabetes Research & Care ◽

10.1136/bmjdrc-2019-000725 ◽

2019 ◽

Vol 7 (1) ◽

pp. e000725 ◽

Cited By ~ 7

Author(s):

Gian Paolo Fadini ◽

Mayur Sarangdhar ◽

Fabrizio De Ponti ◽

Angelo Avogaro ◽

Emanuel Raschi

Keyword(s):

Reporting System ◽

Immunosuppressive Drugs ◽

Fournier’S Gangrene ◽

Rare Occurrence ◽

Fournier's Gangrene ◽

Glucose Lowering ◽

Sodium Glucose Cotransporter ◽

Definition Of ◽

Reporting Frequency ◽

Design And Methods

ObjectiveSodium glucose cotransporter-2 inhibitors (SGLT2i) exert cardiorenal protection in people with diabetes. By inducing glycosuria, SGLT2i predispose to genital infections. In addition, rare occurrence of Fournier’s gangrene (FG) has been reported. We aimed to investigate such association through the U.S. Food and Drug Administration (FDA) adverse event (AE) reporting system (FAERS).Research design and methodsWe mined the FAERS up to 2018q3 (before FDA warning about SGLT2i-associated FG) to retrieve reports including FG as an AE and SGLT2i as suspect or concomitant drugs, and calculated proportional reporting ratios (PRR).ResultsWe retrieved 47 cases of FG and 17 cases of other severe AEs of the genital area associated with SGLT2i. Patients with FG were ~10 years older than those with other severe genital AEs. Overall, 77% occurred in men. Three patients were concomitantly treated with systemic immunosuppressive drugs. Increased reporting frequency emerged for SGLT2i compared with other drugs, with a PRR ranging from 5 to 10. The disproportional reporting of FG with SGLT2i remained robust and consistently significant when restricting to the period when SGLT2i were available, to reports filed for glucose-lowering medications or for drugs with the diabetes indication, and after refining the definition of FG. FG was disproportionally associated with psoriasis and with the combination of immunosuppressants and SGLT2i.ConclusionsAlthough causality cannot be demonstrated, SGLT2i may predispose to FG and other severe genital AEs. Since the use of SGLT2i is expected to increase significantly, clinicians should be aware of these severe, although rare, AEs and their predisposing factors.

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Real-world evidence analysis of the impact of steroid-eluting implants on healthcare resource use among chronic rhinosinusitis patients undergoing sinus surgery

Current Medical Research and Opinion ◽

10.1080/03007995.2021.2022874 ◽

2021 ◽

pp. 1-12

Author(s):

Veena Hoffman ◽

Kathleen M. Mortimer ◽

Kyra Mulder ◽

Ia Topuria ◽

Richard Gliklich ◽

...

Keyword(s):

Chronic Rhinosinusitis ◽

Resource Use ◽

Real World ◽

Healthcare Resource ◽

Sinus Surgery ◽

Healthcare Resource Use ◽

Real World Evidence ◽

Evidence Analysis ◽

The Impact

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The range of bicycle helmet performance at real world impact locations

Proceedings of the Institution of Mechanical Engineers Part P Journal of Sports Engineering and Technology ◽

10.1177/17543371211057721 ◽

2021 ◽

pp. 175433712110577

Author(s):

Ann R Harlos ◽

Steven Rowson

Keyword(s):

Real World ◽

Test Line ◽

Linear Acceleration ◽

The United States ◽

Consumer Product Safety Commission ◽

Bicycle Helmets ◽

Impact Location ◽

Increased Risk ◽

Post Hoc ◽

The Impact

In the United States, all bicycle helmets must comply with the standard created by the Consumer Product Safety Commission (CPSC). In this standard, bike helmets are only required to by tested above an established test line. Unregulated helmet performance below the test line could pose an increased risk of head injury to riders. This study quantified the impact locations of damaged bike helmets from real-world accidents and tested the most commonly impacted locations under CPSC bike helmet testing protocol. Ninety-five real-world impact locations were quantified. The most common impact locations were side-middle (31.6%), rear boss-rim (13.7%), front boss-rim (9.5%), front boss-middle (9.5%), and rear boss-middle (9.5%). The side-middle, rear boss-rim, and front boss (front boss-middle and front boss-rim regions combined) were used for testing. Two of the most commonly impacted regions were below the test line (front boss-rim and rear boss-rim). Twelve purchased helmet models were tested under CPSC protocol at each location for a total of 36 impacts. An ANOVA test showed that impact location had a strong influence on the variance of peak linear acceleration (PLA) ( p = 0.002). A Tukey HSD post hoc test determined that PLA at the side-middle (214.9 ± 20.8 g) and front boss (228.0 ± 39.6 g) locations were significantly higher than the PLA at the rear boss-rim (191.5 ± 24.2 g) location. The highest recorded PLA (318.8 g) was at the front boss-rim region. This was the only test that exceeded the 300 g threshold. This study presented a method for quantifying real-world impact locations of damaged bike helmets. Higher variance in helmet performance was found at the regions on or below the test line than at the region above the test line.

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P1.16-07 Real World Evidence of the Impact of Immunotherapy in Patients with Advanced Lung Cancer

Journal of Thoracic Oncology ◽

10.1016/j.jtho.2019.08.1233 ◽

2019 ◽

Vol 14 (10) ◽

pp. S588

Author(s):

C. Pettengell ◽

J. Law ◽

L. Le ◽

M. Sung ◽

S. Lau ◽

...

Keyword(s):

Lung Cancer ◽

Real World ◽

Advanced Lung Cancer ◽

Real World Evidence ◽

The Impact

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Evaluating probiotics for the prevention of ventilator-associated pneumonia: a randomised placebo-controlled multicentre trial protocol and statistical analysis plan for PROSPECT

BMJ Open ◽

10.1136/bmjopen-2018-025228 ◽

2019 ◽

Vol 9 (6) ◽

pp. e025228 ◽

Cited By ~ 6

Author(s):

Jennie Johnstone ◽

Diane Heels-Ansdell ◽

Lehana Thabane ◽

Maureen Meade ◽

John Marshall ◽

...

Keyword(s):

Statistical Analysis ◽

Critically Ill ◽

Critically Ill Patients ◽

Controlled Trial ◽

Statistical Analysis Plan ◽

Hospital Length Of Stay ◽

Sensitivity Analyses ◽

Ventilator Associated Pneumonia ◽

Increased Risk ◽

The Impact

IntroductionVentilator-associated pneumonia (VAP) is the most common healthcare-associated infection in critically ill patients. Prior studies suggest that probiotics may reduce VAP and other infections in critically ill patients; however, most previous randomised trials were small, single centre studies. The Probiotics: Prevention of Severe Pneumonia and Endotracheal Colonization Trial (PROSPECT) aims to determine the impact of the probioticLactobacillus rhamnosusGG on VAP and other clinically important outcomes in critically ill adults.MethodsPROSPECT is a multicentre, concealed, randomised, stratified, blinded, controlled trial in patients ≥18 years old, anticipated to be mechanically ventilated ≥72 hours, in intensive care units (ICUs) in Canada, the USA and Saudi Arabia. Patients receive either 1×1010 colony forming units ofL. rhamnosusGG twice daily or an identical appearing placebo. Those at increased risk of probiotic infection are excluded. The primary outcome is VAP. Secondary outcomes are other ICU-acquired infections includingClostridioides difficileinfection, diarrhoea (including antibiotic-associated diarrhoea), antimicrobial use, ICU and hospital length of stay and mortality. The planned sample size of 2650 patients is based on an estimated 15% VAP rate and will provide 80% power to detect a 25% relative risk reduction.Ethics and disseminationThis protocol and statistical analysis plan outlines the methodology, primary and secondary analyses, sensitivity analyses and subgroup analyses. PROSPECT is approved by Health Canada (#9427-M1133-45C), the research ethics boards of all participating hospitals and Public Health Ontario. Results will be disseminated via academic channels (peer reviewed journal publications, professional healthcare fora including international conferences) and conventional and social media. The results of PROSPECT will inform practice guidelines worldwide.Trialregistration numberNCT02462590; Pre-results.

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