-
BMJ (Clinical Research Ed.) Jun 2024To evaluate the comparative effectiveness of sodium-glucose cotransporter-2 (SGLT-2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and dipeptidyl... (Comparative Study)
Comparative Study
SGLT-2 inhibitors, GLP-1 receptor agonists, and DPP-4 inhibitors and risk of hyperkalemia among people with type 2 diabetes in clinical practice: population based cohort study.
OBJECTIVES
To evaluate the comparative effectiveness of sodium-glucose cotransporter-2 (SGLT-2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and dipeptidyl peptidase-4 (DPP-4) inhibitors in preventing hyperkalemia in people with type 2 diabetes in routine clinical practice.
DESIGN
Population based cohort study with active-comparator, new user design.
SETTING
Claims data from Medicare and two large commercial insurance databases in the United States from April 2013 to April 2022.
PARTICIPANTS
1:1 propensity score matched adults with type 2 diabetes newly starting SGLT-2 inhibitors versus DPP-4 inhibitors (n=778 908), GLP-1 receptor agonists versus DPP-4 inhibitors (n=729 820), and SGLT-2 inhibitors versus GLP-1 receptor agonists (n=873 460).
MAIN OUTCOME MEASURES
Hyperkalemia diagnosis in the inpatient or outpatient setting. Secondary outcomes were hyperkalemia defined as serum potassium levels ≥5.5 mmol/L and hyperkalemia diagnosis in the inpatient or emergency department setting.
RESULTS
Starting SGLT-2 inhibitor treatment was associated with a lower rate of hyperkalemia than DPP-4 inhibitor treatment (hazard ratio 0.75, 95% confidence interval (CI) 0.73 to 0.78) and a slight reduction in rate compared with GLP-1 receptor agonists (0.92, 0.89 to 0.95). Use of GLP-1 receptor agonists was associated with a lower rate of hyperkalemia than DPP-4 inhibitors (0.79, 0.77 to 0.82). The three year absolute risk was 2.4% (95% CI 2.1% to 2.7%) lower for SGLT-2 inhibitors than DPP-4 inhibitors (4.6% 7.0%), 1.8% (1.4% to 2.1%) lower for GLP-1 receptor agonists than DPP-4 inhibitors (5.7% 7.5%), and 1.2% (0.9% to 1.5%) lower for SGLT-2 inhibitors than GLP-1 receptor agonists (4.7% 6.0%). Findings were consistent for the secondary outcomes and among subgroups defined by age, sex, race, medical conditions, other drug use, and hemoglobin A1c levels on the relative scale. Benefits for SGLT-2 inhibitors and GLP-1 receptor agonists on the absolute scale were largest for those with heart failure, chronic kidney disease, or those using mineralocorticoid receptor antagonists. Compared with DPP-4 inhibitors, the lower rate of hyperkalemia was consistently observed across individual agents in the SGLT-2 inhibitor (canagliflozin, dapagliflozin, empagliflozin) and GLP-1 receptor agonist (dulaglutide, exenatide, liraglutide, semaglutide) classes.
CONCLUSIONS
In people with type 2 diabetes, SGLT-2 inhibitors and GLP-1 receptor agonists were associated with a lower risk of hyperkalemia than DPP-4 inhibitors in the overall population and across relevant subgroups. The consistency of associations among individual agents in the SGLT-2 inhibitor and GLP-1 receptor agonist classes suggests a class effect. These ancillary benefits of SGLT-2 inhibitors and GLP-1 receptor agonists further support their use in people with type 2 diabetes, especially in those at risk of hyperkalemia.
Topics: Humans; Diabetes Mellitus, Type 2; Hyperkalemia; Sodium-Glucose Transporter 2 Inhibitors; Dipeptidyl-Peptidase IV Inhibitors; Male; Female; Glucagon-Like Peptide-1 Receptor; Aged; Middle Aged; United States; Cohort Studies; Hypoglycemic Agents; Propensity Score; Glucagon-Like Peptide-1 Receptor Agonists
PubMed: 38925801
DOI: 10.1136/bmj-2023-078483 -
Biochemical and Biophysical Research... Jun 2024A hallmark of Alzheimer's disease (AD) is amyloid-β (Aβ) plaque deposition in the brain, causing deficits in cognitive function. Amyloid-beta oligomers (AβOs), the...
A hallmark of Alzheimer's disease (AD) is amyloid-β (Aβ) plaque deposition in the brain, causing deficits in cognitive function. Amyloid-beta oligomers (AβOs), the soluble precursor peptides producing Aβ plaques, also produce neurotoxicity and microgliosis together with glycolytic reprogramming. Recently, monocarboxylate transporter 1 (MCT1), a key glycolysis regulator, and its ancillary protein, CD147, are found to play an important role in the secretion of exosomes, 30-200 nm vesicles in size, which are considered as toxic molecule carriers in AD. However, the effect of low-concentration AβOs (1 nM) on microglia MCT1 and CD147 expression as well as 1 nM AβOs-treated microglia-derived exosomes on neuronal toxicity remain largely elusive. In this study, 1 nM AβOs induce significant axonopathy and microgliosis. Furthermore, 1 nM AβOs-treated neurons- or microglia-derived exosomes produce axonopathy through their autologous or heterologous uptake by neurons, supporting the role of exosomes as neurotoxicity mediators in AD. Interestingly, MCT1 and CD147 are enhanced in microglia by treatment with 1 nM AβOs or exosomes from 1 nM AβOs-treated- microglia or neurons, suggesting the implication of AβOs-induced enhanced MCT1 and CD147 in microglia with AD neuropathogenesis, which is consistent with the in-silico analysis of the single cell RNA sequencing data from microglia in mouse models of AD and AD patients.
PubMed: 38924962
DOI: 10.1016/j.bbrc.2024.150312 -
Postgraduate Medical Journal Jun 2024Tight control of type 2 diabetes (T2DM) in frail older adults has shown to be associated with adverse outcomes. The objective of this study is to determine the...
BACKGROUND
Tight control of type 2 diabetes (T2DM) in frail older adults has shown to be associated with adverse outcomes. The objective of this study is to determine the prevalence of tight glycemic control based on underlying frailty status and its association with functional and cognitive measures in community-dwelling older adults.
METHODOLOGY
Ancillary study of the Singapore Population Health Studies on older adults aged ≥65 years with T2DM. Tight glycemic control cut-offs were based on the 2019 Endocrine Society guideline using HbA1c target range based on a patient's overall health status measured by the FRAIL scale. Data on basic demographics, frailty, cognitive, and functional statuses were collected. Multivariable regression was used to assess potential factors associated with tight glycemic control.
RESULTS
Of 172 community-dwelling older adults with diabetes mellitus and HbA1c done, frail (65%) and pre-frail (64.4%) participants were more likely to have tight glycemic control than robust participants (31.6%, P < 0.001). In multi-variate analysis, frailty (OR 6.43, 95% CI 1.08-38.1, P = 0.041), better cognition (OR 1.15, 95% CI 1.02-1.32, P = 0.028), and multi-morbidity (OR 7.36, 95% CI 1.07-50.4, P = 0.042) were found to be significantly associated with increased odds of tight glycemic control.
CONCLUSION
Tight glycemic control was highly prevalent in frail and pre-frail older adults, especially in those with multi-morbidity and better cognition. Future prospective longitudinal studies are required to evaluate effectiveness of frailty screening in making treatment decisions and long-term outcomes. Key messages What is already known on this topic: There is growing recognition that glycemic targets should be adjusted based on health or frailty status. However, there is no consensus on how health status or frailty should be defined when determining glycemic control targets. What this study adds: Our study found that tight glycemic control was highly prevalent in frail and pre-frail older adults. Our findings highlight the importance of assessing for tight glycemic control based on frailty status and further work is needed to aid implementation of screening and intervention policies to avoid the attendant harms of tight glycemic control.
PubMed: 38924725
DOI: 10.1093/postmj/qgae077 -
Journal of Diabetes Jul 2024We studied the prevalence and incidence of type 2 diabetes (T2DM) and its associated risk factors in younger (20 and 39 years) and older individuals (≥40 years)...
BACKGROUND
We studied the prevalence and incidence of type 2 diabetes (T2DM) and its associated risk factors in younger (20 and 39 years) and older individuals (≥40 years) over a 10-year period.
METHODS
Epidemiological surveys in 2006 (n = 7066) and 2016 (n = 9848) were conducted in similar urban and rural locations of southern India among people aged ≥20 years. Diagnosis of T2DM was made using World Health Organization criteria. Self-reported diabetes was verified from medical records. Age and gender standardized prevalence and incidence rates, percentage change in obesity, hypertension, and dyslipidemia were calculated. Prevalence ratios (PR) were calculated using Poisson regression analyses. Primary study was registered on www.
CLINICALTRIALS
gov. Identifier: NCT03490136.
RESULTS
In 10 years, the prevalence of T2DM increased in younger (7.8% vs. 4.5%, p < 0.0001) and older individuals (34% vs. 28.4%, p < 0.0001). After adjusting for age, family history of diabetes, and waist circumference, younger individuals showed a higher percentage increase in prevalence than the older group (PR = 1.36 [95% confidence interval [CI], 1.14-1.62], p = 0.001) versus (PR = 1.11 [95% CI, 1.02-1.20], p = 0.02). Increase in rates of obesity and dyslipidemia was also higher in the younger than in the older individuals. In 10 years, incidence of T2DM increased by 120% (1.1% vs. 0.5%, p < 0.0001) and 150% (5% vs. 2%, p < 0.0001) in the younger and older individuals, respectively.
CONCLUSIONS
Higher percentage increase in prevalence of T2DM was seen among younger individuals over a 10-year period. Obesity and family history of diabetes were shown to be the primary contributing factors for the rise in prevalence.
Topics: Adult; Female; Humans; Male; Middle Aged; Young Adult; Age Factors; Diabetes Mellitus, Type 2; Dyslipidemias; Incidence; India; Obesity; Prevalence; Risk Factors
PubMed: 38923743
DOI: 10.1111/1753-0407.13576 -
Current Opinion in Ophthalmology Jun 2024This review aims to enhance understanding of juvenile Sjögren's disease (jSjD) by exploring diagnostic criteria, ocular clinical features, ancillary ophthalmic testing,...
PURPOSE OF REVIEW
This review aims to enhance understanding of juvenile Sjögren's disease (jSjD) by exploring diagnostic criteria, ocular clinical features, ancillary ophthalmic testing, and management strategies specific to this rare pediatric condition.
RECENT FINDINGS
Unlike adults, children with jSjD often present with recurrent parotitis and extra-glandular symptoms before developing sicca symptoms. Adult SjD classification criteria do not consider pediatric-specific symptoms and physiological differences. Underutilization of diagnostic tests such as the ocular staining score (OSS) and Schirmer I may result in an incomplete understanding of the prevalence of keratoconjunctivitis sicca in jSjD.
SUMMARY
Timely referral to an ophthalmologist can address perceived feasibility issues with respect to ocular features in jSjD. Management of keratoconjunctivitis sicca in jSjD includes improving ocular surface lubrication and decreasing inflammation. Recognition of pediatric-specific clinical features and development of universally accepted jSjD classification criteria will allow for better identification of potential participants for future jSjD studies.
PubMed: 38923442
DOI: 10.1097/ICU.0000000000001069 -
Scientific Reports Jun 2024Studies in Western populations have shown that Black and Hispanic patients have an earlier age of Multiple Sclerosis (MS) onset and a more severe disease course... (Comparative Study)
Comparative Study Observational Study
Studies in Western populations have shown that Black and Hispanic patients have an earlier age of Multiple Sclerosis (MS) onset and a more severe disease course characterised by faster disability accrual compared to Whites. It is yet unclear whether MS disease characteristics and clinical course differ amongst Asian racial groups. Singapore is uniquely poised to investigate this as its multi-racial population comprises three genetically diverse Asian racial groups-Chinese, Malay and South Asian. Herein, we sought to elucidate differences in the clinical phenotypes, disease-modifying therapy (DMT) usage, and disease course amongst these three Asian racial groups by performinga retrospective observational study on MS patients seen at the National Neuroscience Institute, Singapore. Data on demographics, disease characteristics, ancillary investigations, and DMT usage were collected. One hundred and eighty-eight patients were included (90 Chinese, 32 Malay, and 66 South Asian). Our findings showed that MS prevalence was the highest in South Asians followed by Malays and Chinese, while demographics, healthcare access, and longer-term disease course were identical across the racial groups. However, several differences and trends were elucidated: (1) South Asian patients had milder sentinel attacks (p = 0.006), (2) a higher proportion of Malay patients had enhancing lesions on their initial MRI (p = 0.057) and the lesion topography differed across the races (p = 0.034), and (3) more Malay patients switched out of their initial DMT (p = 0.051). In conclusion, MS disease characteristics were largely similar across these three Asian racial groups, and while there were some clinical and radiological differences at presentation, these did not influence longer-term outcomes.
Topics: Humans; Singapore; Male; Female; Multiple Sclerosis; Adult; Retrospective Studies; Asian People; Middle Aged; Prevalence; Magnetic Resonance Imaging
PubMed: 38918591
DOI: 10.1038/s41598-024-65575-3 -
Cureus May 2024Artificial intelligence (AI) is a suite of technologies that enables computers to learn and interpret information like human cognition. It has found applications across...
Artificial intelligence (AI) is a suite of technologies that enables computers to learn and interpret information like human cognition. It has found applications across various fields, including healthcare, agriculture, astronomy, navigation, and robotics. Within healthcare, AI has the potential to enhance diagnostic accuracy, facilitate drug research, and automate patient experiences. This comparative study focuses on the proficiency of AI in generating accurate differential diagnoses in the field of pathology. Six medical vignettes were crafted, and each scenario was then input into three different AI platforms. The pathologist reviewed and determined the most accurate AI model.
PubMed: 38915984
DOI: 10.7759/cureus.61075 -
European Stroke Journal Jun 2024Atrial fibrillation (AF) and cancer are each associated with worse outcomes in patients with acute ischemic stroke (AIS). Few studies have evaluated the impact of AF on...
INTRODUCTION
Atrial fibrillation (AF) and cancer are each associated with worse outcomes in patients with acute ischemic stroke (AIS). Few studies have evaluated the impact of AF on outcomes of cancer-related stroke.
PATIENTS AND METHODS
We conducted a retrospective cross-sectional study using the 2016-2019 National Inpatient Sample, identifying all hospitalizations with diagnosis codes for cancer and AIS. The primary exposure was a diagnosis of AF. The primary outcome was in-hospital mortality. The secondary outcomes were length-of-stay and discharge to non-home locations. We used multiple logistic and linear regression models, adjusted for age, gender, race-ethnicity, and the Charlson Comorbidity Index, to examine the association between AF and study outcomes.
RESULTS
Among 150,200 hospitalizations with diagnoses of cancer and AIS (mean age 72 years, 53% male), 40,084 (26.7%) included comorbid AF. Compared to hospitalizations without AF, hospitalizations with AF had higher rates of in-hospital mortality (14.8% [95% CI, 14.0%-15.6%] vs 12.1% [95% CI, 11.6%-12.5%]) and non-home discharge disposition (83.5% [95% CI, 82.7%-84.3%] vs 75.1% [95% CI, 74.5%-75.7%]) as well as longer mean length-of-stay (8.4 days [95% CI, 8.2-8.6 days] vs 8.2 days [95% CI, 8.0-8.3 days]). In multivariable analyses, AF remained independently associated with higher odds of in-hospital mortality (adjusted odds ratio [aOR], 1.34; 95% CI, 1.24-1.46), non-home discharge disposition (aOR, 1.32; 95% CI, 1.23-1.42), and longer length-of-stay (adjusted mean difference, 13.7%; 95% CI, 10.9%-16.7%).
DISCUSSION AND CONCLUSION
In cancer-related AIS, comorbid AF is associated with worse short-term outcomes, including higher odds for in-hospital mortality, poor discharge disposition, and longer hospital stays.
PubMed: 38915252
DOI: 10.1177/23969873241263402 -
Human Pathology Jun 2024Multiple myeloma (MM) is an incurable malignant plasma cell neoplasm, representing the second most common hematopoietic cancer. As plasma cell neoplasms are clonal and...
Multiple myeloma (MM) is an incurable malignant plasma cell neoplasm, representing the second most common hematopoietic cancer. As plasma cell neoplasms are clonal and often secrete a monoclonal protein (M-spike), laboratory diagnosis is usually straightforward, especially when ancillary studies such as immunohistochemistry, flow cytometry, and protein electrophoresis are available in addition to microscopic examination. Despite the repertoire of diagnostic tools, rare cases pose diagnostic dilemmas, especially when reagent antibodies do not react as expected, extent of disease is patchy, or when disease occurs in unique age groups. In this retrospective study, we report a series of challenging diagnostic cases, discussing aberrant findings and comparing them to more classic counterparts. Twelve cases collected during routine clinical sign-out were reanalyzed and include examples of MGUS, classic multiple myeloma, t(11;14) rearranged myeloma, minimal residual disease, AA and AL amyloidosis, truncated light chain, non-secretory and non-producer myeloma, biphenotypic myeloma, oligoclonal expansion after bone marrow transplant, and plasma cell leukemia in a young adult. This cohort showcases the diversity of atypical presentations of plasma cell neoplasms, and we highlight standardized approaches to workup to avoid diagnostic pitfalls.
PubMed: 38909710
DOI: 10.1016/j.humpath.2024.06.012 -
Sleep Health Jun 2024To examine the association of biopsychosocial stress indicators (perceived stress, perceived discrimination, stressful life events, and allostatic load) with sleep...
OBJECTIVES
To examine the association of biopsychosocial stress indicators (perceived stress, perceived discrimination, stressful life events, and allostatic load) with sleep outcomes (sleep duration and insomnia symptoms) and to examine sex and age interactions for associations between stress and sleep in older Puerto Rican adults.
METHODS
Secondary analyses were performed with 830 participants (72% female) from wave 2 (2006-2011) of the Boston Puerto Rican Health Study (BPRHS), a prospective population-based cohort study (45-75years at baseline) and Boston Puerto Rican Osteoporosis Study (BPROS) (2007-2012), an ancillary study of the BPRHS. Recruitment occurred in randomly selected census blocks using door-to-door and community-based activities. In-home data collection visits included a baseline assessment and follow-up interviews. Questionnaires assessed perceived stress, discrimination, stressful life events, and sleep. Allostatic load indicators were measured objectively. Regression models controlled for sociodemographic, behavioral, and health factors, with interaction analyses, followed by sex- and sex-by-age-stratified analyses.
RESULTS
In the prior 2years, participants with chronic stress had 50% greater odds of reporting nonoptimal sleep duration (<7 or >9 hours). Life events trajectories were significantly related to insomnia symptoms. Men ≥65years who experienced chronic stress had greater insomnia symptoms than women, or than men with low stress or acute stress.
CONCLUSIONS
Stressful life events may affect sleep duration and insomnia symptoms among older Puerto Rican adults, particularly men 65 years and older who experienced chronic stress. Given the differences in sleep patterns experienced by older adults and their relationships with health outcomes, identifying methods to support sleep health among those with chronic stress is important.
PubMed: 38908940
DOI: 10.1016/j.sleh.2024.04.001