Aims
To conduct a systematic literature review to identify recent epidemiological, biomarker, genetic and clinical evidence that expands our understanding of nonalcoholic fatty liver disease (NAFLD) ...as a metabolic disorder.
Materials and Methods
We performed a literature search using PubMed to identify trials, observational studies and meta‐analyses published in the past 5 years.
Results
A total of 95 publications met prespecified inclusion criteria and reported on the interplay between NAFLD/nonalcoholic steatohepatitis (NASH) and metabolic dysfunction, in terms of disease burden and/or epidemiology (n = 10), pathophysiology, risk factors and associated conditions (n = 29), diagnosis and biomarkers (n = 34), and treatment approaches (n = 22). There is a growing body of evidence on the links between NAFLD/NASH pathogenesis and mechanisms of metabolic dysfunction, through liver lipid accumulation, insulin resistance, inflammation, apoptosis, and fibrogenic remodelling within the liver. The frequent co‐occurrence of NAFLD with obesity, metabolic syndrome and type 2 diabetes supports this premise. Therapeutic approaches originally envisaged for type 2 diabetes or obesity (such as glucagon‐like peptide‐1 receptor agonists, sodium‐glucose co‐transporter‐2 inhibitors, insulin sensitizers and bariatric surgery) have shown promising signs of benefit for patients with NAFLD/NASH.
Conclusions
Given the complex interplay between NAFLD and metabolic dysfunction, there is an urgent need for multidisciplinary collaboration and established protocols for care of patients with NAFLD that are individualized and ideally support reduction of overall metabolic risk as well as treatment for NASH.
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.
Aim
Fluoroquinolone‐related hypoglycaemia is rare but may become clinically relevant in individuals at high baseline hypoglycaemic risk, such as patients with diabetes using sulphonylureas. Our ...population‐based cohort study assessed whether fluoroquinolones are associated with an increased risk of severe hypoglycaemia compared with amoxicillin among patients treated with sulphonylureas.
Materials and Methods
Using the UK's Clinical Practice Research Datalink Aurum linked to hospitalization and vital statistics data, we assembled a base cohort of patients who initiated second‐generation sulphonylureas (1998‐2020). The study cohort included patients initiating either fluoroquinolones or amoxicillin while on sulphonylureas. Using an intent‐to‐treat exposure definition, we assessed the 30‐day risk of severe hypoglycaemia (hospitalization with or death because of hypoglycaemia) associated with fluoroquinolones compared with amoxicillin. Cox models estimated hazard ratios (HRs) with 95% confidence intervals (CIs) of severe hypoglycaemia after 1:5 matching on previous sulphonylurea use and propensity scores. Secondary analyses were stratified by demographics and glycated haemoglobin.
Results
Overall, 143 417 patients initiated fluoroquinolones (n = 13 123) or amoxicillin (n = 130 294) while on sulphonylureas. Compared with amoxicillin, fluoroquinolones were not associated with the risk of severe hypoglycaemia (HR, 1.17; 95% CI, 0.91‐1.50). Fluoroquinolones were associated with an increased risk in patients <65 years (HR, 2.90; 95% CI, 1.41‐5.97) but not in those ≥65 years (HR, 1.03; 95% CI, 0.79‐1.35) in stratified analyses. There was no evidence of effect modification by sex or glycated haemoglobin.
Conclusions
In patients using second‐generation sulphonylureas, fluoroquinolones were not associated with an increased risk of severe hypoglycaemia compared with amoxicillin. An increased risk among younger adults is possible.
Objective
To investigate whether users of hormonal contraceptives (HCs) are at increased risk of depression compared with non‐users.
Design
Register‐based cohort study.
Setting
Sweden.
Sample
Women ...aged 15–25 years between 2010 and 2017 with no prior antidepressant treatment, psychiatric diagnose or contraindication for HCs (n = 739 585).
Methods
Women with a prescription of HC were identified via the Swedish Prescribed Drug Register (SPDR). Relative risks (RRs) for first depression diagnosis in current HC‐users compared with non‐users were modelled by Poisson regression. Adjustments included age, medical indication for HC‐use and parental history of mental disorders, among others.
Main outcome measures
Depression, captured by a redeemed prescription of antidepressant treatment, or a first depression diagnosis in the SPDR and the National Patient Register.
Results
Compared with non‐users, women on combined oral contraceptives (COCs) and oral progestogen‐only products had lower or no increased risk of depression, relative risk (RR) 0.89 (95% CI 0.87–0.91) and 1.03 (95% CI 0.99–1.06) after adjustments, respectively. Age‐stratified analyses demonstrated that COC use in adolescents conferred no increase in risk (RR 0.96, 95% CI 0.93–0.98), whereas use of progestogen‐only pills (RR 1.13, 95% CI 1.07–1.19), contraceptive patch/vaginal ring (RR 1.43, 95% CI 1.30–1.58), implant (RR 1.38, 95% CI 1.30–1.45) or a levonorgestrel intrauterine device (RR 1.59, 95% CI 1.46–1.73) were associated with increased risks.
Conclusions
This study did not find any association between use of COCs, which is the dominating HC in first time users, and depression. Non‐oral products were associated with increased risks. Residual confounding must be addressed in the interpretation of the results.
Tweetable
There is no association between combined hormonal contraceptives and depression.
Tweetable
There is no association between combined hormonal contraceptives and depression.
Real‐world epidemiology gives us the unique opportunity to observe large numbers of people, and the actions and events that characterize their encounters with healthcare providers. However, the ...heterogeneity and sheer diversity of the population and healthcare systems makes it impossible for researchers to compare “like with like” when attempting to draw causal inferences about interventions and outcomes. The critical issue in epidemiological datasets relates to high risk of bias due to confounders that stem from baseline differences between groups. Propensity score (PS) techniques are statistical approaches that have been used to tackle potential imbalance in the comparison groups. The PS is the estimated probability (based on measured baseline covariates) that the patient receives a particular intervention. Patients that share similar PS will most likely have the same distributions of underlying covariates included in the PS. Implementation of PS methods may achieve better balance of covariates, but there is no consensus on the best way of capturing all relevant confounders for incorporation into the PS model. Should covariates be selected by clinical or epidemiological experts, or would data‐driven algorithms (machine learning) offer more efficient and reliable methods of estimating PS and controlling for confounding? The PS can be incorporated into the analysis in different ways, each with its own strengths and limitations, and researchers must choose the best fit for their study objectives. PS methods are particularly advantageous in situations where there are large numbers of measured covariates but relatively few outcome events captured in healthcare administrative databases.
With the widespread use of electronic medical records and administrative claims databases, analytic results from so‐called real‐world data have become increasingly important in healthcare ...decision‐making. Diabetes mellitus is a heterogeneous condition that involves a broad spectrum of patients. Real‐world database studies have been recognised as a powerful tool to understand the impact of current practices on clinical courses and outcomes, such as long‐term glucose control, development of microvascular or macro‐vascular diseases, and mortality. Diabetes is also a major global health issue and poses a significant social and economic burden worldwide. Therefore, it is critical to understand the epidemiology, clinical course, treatment reality, and long‐term outcomes of diabetes to determine realistic solutions to a variety of disease‐related issues that we are facing. In the present review, we summarise the healthcare system and large‐scale databases currently available in Japan, introduce the results from recent database studies involving Japanese patients with diabetes, and discuss future opportunities and challenges for the use of databases in the management of diabetes.
Sodium‐glucose co‐transporter‐2 (SGLT2) inhibitors are widely prescribed in people with type 2 diabetes. We aimed to investigate whether SGLT2 inhibitor prescription is associated with COVID‐19, when ...compared with an active comparator. We performed a propensity‐score‐matched cohort study with active comparators and a negative control outcome in a large UK‐based primary care dataset. Participants prescribed SGLT2 inhibitors (n = 9948) and a comparator group prescribed dipeptidyl peptidase‐4 (DPP‐4) inhibitors (n = 14 917) were followed up from January 30 to July 27, 2020. The primary outcome was confirmed or clinically suspected COVID‐19. The incidence rate of COVID‐19 was 19.7/1000 person‐years among users of SGLT2 inhibitors and 24.7/1000 person‐years among propensity‐score‐matched users of DPP‐4 inhibitors. The adjusted hazard ratio was 0.92 (95% confidence interval 0.66 to 1.29), and there was no evidence of residual confounding in the negative control analysis. We did not observe an increased risk of COVID‐19 in primary care amongst those prescribed SGLT2 inhibitors compared to DPP‐4 inhibitors, suggesting that clinicians may safely use these agents in the everyday care of people with type 2 diabetes during the COVID‐19 pandemic.
Objectives
To examine age‐related trajectories of cardiovascular risk and use of aspirin and statin among U.S. adults aged 50 or older.
Design
Repeated cross‐sectional study using data from 2011 to ...2018 National Health and Nutrition Examination Surveys.
Setting
Nationally representative health interview survey in the United States.
Participants
Non‐institutionalized adults aged 50 years and older (n = 11,392 unweighted).
Measurements
Primary prevention was defined as the prevention of a first cardiovascular event including coronary heart disease, angina/angina pectoris, heart attack, or stroke, whereas secondary prevention was defined as those with a history of these clinical conditions. Medication use was determined by self‐report; aspirin use included dose and frequency, and statin use included generic names, days of prescription fills, and indications. We examined linear trends between age and each medication use, after controlling for period, sex, and race/ethnicity.
Results
Prevalence of those eligible for primary prevention treatment increased with age from 31.8% in ages 50–54 to 52.0% in ages ≥75 (p < 0.001). Similarly, those eligible for secondary prevention treatment increased with age from 2.7% in ages 50–54 to 21.1% in ages ≥75 (p < 0.001). Low‐dose daily aspirin use increased with age (p < 0.001), and 45.3% of adults aged ≥75 took low‐dose aspirin daily for primary prevention. Statin use also increased with age (p < 0.001), and 56.4% of adults aged ≥75 had long‐term statin use for secondary prevention.
Conclusion
While adults aged ≥75 do not benefit from the use of aspirin to prevent the first CVD, many continue to take aspirin on a regular basis. In spite of the clear benefit of statin use to prevent a subsequent CVD event, many older adults in this risk category are not taking a statin. Further education and guidance for both healthcare providers and older adults regarding the appropriate use of aspirin and statins to prevent CVD is needed.
Aim
The objective of this study was to describe the use of COVID‐19‐related medicines during pregnancy and their evolution between the early/late periods of the pandemic.
Methods
Pregnant women who ...tested positive for SARS‐CoV‐2 from March 2020 to July 2021 were included using the COVI‐PREG registry. Exposure to the following COVID‐19‐related medicines was recorded: antibiotics, antivirals, hydroxychloroquine, corticosteroids, anti‐interleukin‐6 and immunoglobulins. We described the prevalence of medicines used, by trimester of pregnancy, maternal COVID‐19 severity level and early/late period of the pandemic (before and after 1 July 2020).
Findings
We included 1964 pregnant patients who tested positive for SARS‐CoV‐2. Overall, 10.4% (205/1964) received at least one COVID‐19‐related medicine including antibiotics (8.6%; 169/1694), corticosteroids (3.2%; 62/1964), antivirals (2.0%; 39/1964), hydroxychloroquine (1.4%; 27/1964) and anti‐interleukin‐6 (0.3%; 5/1964). The use of at least one COVID‐19‐related medicine was 3.1% (12/381) in asymptomatic individuals, 4.2% (52/1233) in outpatients, 19.7% (46/233) in inpatients without oxygen, 72.1% (44/61) in those requiring standard oxygen, 95.7% (22/23) in those requiring high flow oxygen, 96.2% (25/26) in patients who required intubation and 57.1% (4/7) among patients who died. The proportion who received medicines to treat COVID‐19 was higher before than after July 2020 (16.7% vs. 7.7%). Antibiotics, antivirals and hydroxychloroquine had lower rates of use during the late period.
Conclusion
Medicine use in pregnancy increased with disease severity. The trend towards increased use of corticosteroids seems to be aligned with changing guidelines. Evidence is still needed regarding the effectiveness and safety of COVID‐19‐related medicines in pregnancy.
Aim
To reproduce and correct studies on bariatric surgery and the reduction in major adverse cardiovascular events (MACE) among patients with obesity and type 2 diabetes (T2D).
Methods
We used ...electronic healthcare records (EHR) from in and outpatient facilities around the United States to identify a cohort of patients with T2D, aged 18 to 80 years and with a body mass index (BMI) of 30 kg/m2 or higher undergoing bariatric surgery. We compared against hip/knee arthroplasty to establish an active comparison group that reduced bias from differential information and confounding. The main outcome was six‐point MACE. Pre‐exposure characteristics were adjusted in propensity score (PS) models with 1:2 matching plus high‐dimensional PS matching.
Results
After a range of exclusions, the final cohort included 344 bariatric surgery patients (65% female; mean age 58 years) and 551 PS‐matched patients undergoing arthroplasty (65% female; 59 years). Median follow‐up was 2.5 years in both groups. Bariatric surgery patients showed a sustained 20% weight reduction and an HbA1c reduction by 1% point. We found no benefits of bariatric surgery for six‐point MACE (HR = 0.99; 95% CI 0.76‐1.30). We observed known increases in risks for vitamin B12 deficiency anaemia (HR = 3.06; 1.10‐8.49) and cholelithiasis (HR = 1.72; 0.94‐3.13).
Conclusions
This real‐world evidence study found reductions in HbA1c and BMI following bariatric surgery similar to trials, and no meaningful cardiovascular benefit compatible with the underpowered trials but in contrast to earlier EHR studies. We showed how information bias typical in EHR analyses and confounding may cause substantial bias.
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