Association between Plant-based Diet and Risk of Chronic Diseases and All-Cause Mortality in Centenarians in China: A Cohort Study.

Background: Numerous studies have suggested the health benefits of a plant-based dietary pattern. However, whether this dietary pattern is associated with health benefits for centenarians remains unexplored. Our study aimed to investigate the correlation between 16 widely consumed Chinese food items and the incidence rates of chronic diseases and all-cause mortality among centenarians. Methods: We conducted a dietary survey on 3372 centenarians with an average age of 102.33 y in China. After rigorous screening, we identified 2675 centenarians, who underwent a 10-y follow-up study with all-cause mortality as the primary outcome. We developed 6 dietary patterns on the basis of the food consumption frequency of each participant. To model the impact of missing values, we employed multiple imputation methods, verifying the robustness of models. Results: The overall plant-based diet index (PDI), healthy plant-based diet index (hPDI), unhealthy plant-based diet index (uPDI), healthy plant-based foods index (HPF), unhealthy plant-based foods index (uHPF), and animal-based foods index (AF) scores among centenarians in China were 46.95 ± 6.29, 44.43 ± 5.76, 51.09 ± 6.26, 21.63 ± 4.79, 9.91 ± 2.41, and 14.59 ± 3.58, respectively. High scores of PDI, hPDI, and HPF were associated with a lower risk of chronic diseases. In the 10-y follow-up study, 92.90% of centenarians have died. The high scores of the PDI (HRPDI = 0.81), hPDI (HRhPDI = 0.79), and HPF (HRHPF = 0.81) scores were significantly associated with a lower risk of death compared with the low scores. Conversely, the high AF score (HRAF = 1.17) was significantly associated with a higher risk of death compared with the low scores. Conclusion: Despite the fact that a higher score in both a predominantly plant-based dietary pattern and a healthy dietary pattern can decrease the death among centenarians, not all HPFs have this effect. A higher AF predicted a higher risk of mortality, whereas higher PDI, hPDI, and HPF were associated with a lower risk of mortality among Chinese centenarians.

Atrial fibrillation increases the risk of all-cause dementia, Alzheimer's disease, and vascular dementia: A cohort study of 373, 415 participants in the UK Biobank.

BACKGROUND: Accumulated evidence has highlighted the association between atrial fibrillation and the risk of developing dementia. METHODS: This current cohort study utilized data from the UK Biobank to explore the association between atrial fibrillation (AF) and all-cause dementia (ACD), encompassing its main subtypes (Alzheimer's disease (AD), and vascular dementia (VD)). Cox proportional hazards models were applied to examine the association of AF and dementia with its primary subtypes after adjusting for different sets of covariates. Hazard ratios (HRs) with 95 % confidential intervals (CIs) were estimated to quantify the associated risks. Competing risk model was applied in sensitivity analysis. RESULTS: After exclusion, 373, 415 participants entered the primary analysis. Among these, 27, 934 (7.48 %) were with a history AF at baseline, while 345, 481 (92.52 %) were without. During a mean follow-up of 13.45 years, ACD was diagnosed in 1215 individuals with AF and 3988 individuals without AF. Participants with AF had higher risks of ACD (1.79 [1.67-1.91]), AD (1.48 [1.32-1.65]), and VD (2.46 [2.17-2.80]) in the fully adjusted Cox regression models. Results of subgroup and sensitivity analyses predominantly aligned with the positive associations in primary analysis. LIMITATIONS: The applicability of our findings to diverse ethnicities might require careful consideration and the behind biological mechanisms need to be further revealed. CONCLUSIONS: It indicated that people with atrial fibrillation had an increased future risk of all-cause dementia, Alzheimer's disease, vascular dementia. Atrial fibrillation screening and prevention strategies should take into account to prevent and delay the onset of dementia.

Ocular toxicities in chimeric antigen receptor T-cell therapy: a real-world study leveraging FAERS database.

Aim: The purpose of this study was to comprehensively explore the ocular toxicity associated with chimeric antigen receptor (CAR) T-cell therapy. Materials & methods: Data were assembled from the US FDA's Adverse Event Reporting System (FAERS) database from 2017 to 2023. Information component and reporting odds ratio methods were used for signal detection in total/categorized CAR T-cell therapy. Results: A total of 17 positive signals (preferred term) were detected, yet none of them were documented in the product information. Some adverse events were with death outcomes and overlapped a lot with cytokine-release syndrome. Conclusion: The ocular adverse events associated with CAR-T cell therapy are noteworthy, and it is imperative to maintain increased alertness and institute early intervention strategies.

CAR-T-cell therapy is a highly effective treatment for blood cancers that has gained significant attention as a promising therapy in recent years. However, a complete analysis of its side effects on eyes has not been determined. In this study, we examined eye-related adverse events with five US Food and Drug Administration (FDA)-approved CAR T-cell therapies by using data from the FDA. We found that certain eye issues such as dilated pupils, impaired pupillary light reflex and eye surface bleeding deserve attention. Surprisingly, these problems were not mentioned in the product information. Since some adverse events can have severe outcomes, it is important to be vigilant and take early action.

Pharmacovigilance analysis of cardiac risks associated with Bruton tyrosine kinase inhibitors.

BACKGROUND: Bruton tyrosine kinase inhibitors (BTKIs) can be associated with several cardiac risks. RESEARCH DESIGN AND METHODS: The study was conducted based on records from a large spontaneous reporting database, the Food and Drug Administration Adverse Event Reporting System, for cardiac events reported for several BTKI agents. Reporting odds ratio and information components based on statistical shrinkage transformation were utilized to measure disproportionality. RESULTS: The final number of records for BTKI-related cardiac events was 10 320. Death or life-threatening events occurred in 17.63% of all associated cardiac records. Significant reporting was captured between BTKI (total/specific) and cardiac events, with the strongest association for ibrutinib. A total of 47 positive signals were evacuated for ibrutinib, with atrial fibrillation being the most commonly reported one. Concomitantly, cardiac failure, congestive, cardiac disorder, arrhythmia, pericardial effusion, and atrial flutter were also noticed for relatively stronger signal and disproportionality. Atrial fibrillation was over-reported in the three groups (ibrutinib, acalabrutinib, and zanubrutinib), and acalabrutinib had statistically significant lower reporting compared with ibrutinib. CONCLUSIONS: Receiving ibrutinib, acalabrutinib, or zanubrutinib might increase the chance of cardiac complications, with ibrutinib posing the highest risk. The type of cardiotoxicity involved in ibrutinib was highly variable.

Updated insights on cardiac risks of CD19-directed chimeric antigen receptor T-cell therapy: a pharmacovigilance study.

Aim: Comprehensively characterize the cardiotoxicity of CD19-directed chimeric antigen receptor T-cell (CAR-T) products. Materials & methods: Data between 2017 and 2021 in the US FDA's Adverse Event Reporting System database were utilized. Disproportionality was measured using reporting odds ratio and information component. Hierarchical clustering analysis was performed to explore the relationships among cardiac events. Results: Tisagenlecleucel exhibited the highest percentage of death (53.24%) and life-threatening (13.39%) outcomes. Axicabtagene ciloleucel and tisagenlecleucel were equal in the number of positive signals (n = 15), while the former had excessive reporting of several cardiac events versus the latter, such as atrial fibrillation, cardiomyopathy, cardiorenal syndrome and sinus bradycardia. Conclusion: Several cardiac risks should be considered for CAR-T treatment and these events might vary in frequency and severity following different CAR-T agents.

Chimeric antigen receptor T-cell (CAR-T) therapy is effective in a wide spectrum of malignancies. However, the complete cardiotoxicity profile associated with this new treatment has not been characterized. This study systematically analyzed the reported cardiac events of four approved CAR-T agents using the US FDA's Adverse Event Reporting System database. It indicated that the type of cardiac events was broad and overlapped a lot with cytokine release syndrome. Pre-therapy assessment, intensive monitoring and appropriate intervention were critical to reduce the level of cardiac damage or the rate of mortality in patients receiving CAR-T.

Longitudinal Relationship Between Frailty and Cognitive Impairment in Chinese Older Adults: A Prospective Study.

We aimed to examine the longitudinal association between frailty and cognitive impairment in the older Chinese population. This prospective cohort study used data from the Chinese Longitudinal Healthy Longevity Study 2011 wave. We calculated the follow-up duration as 3 years from the baseline year. Frailty was measured using the frailty index, and cognitive function was calculated by Mini-Mental State Examination Scale. Participants who were non-frailty and those with normal cognitive function were included in 2011 and followed up in 2014, respectively. Frailty was an independent risk factor for early-onset cognitive impairment. Age, hearing impairment, and a decreased ability to perform daily activities were the main risk factors for cognitive impairment, while affluent economic status was a protective factor. Cognitive impairment was not found to be an independent risk factor for frailty. We concluded that the frailty index is a significant predictor of cognitive impairment among community-dwelling older adults.

Updated Insights on Cardiac and Vascular Risks of Proton Pump Inhibitors: A Real-World Pharmacovigilance Study.

Background: Proton pump inhibitors (PPIs) are among the most widely prescribed medications in clinical practice. However, there are also concerns about the potential risks of long-term PPI use. The present study aimed to examine the safety of PPIs and summarize their potential cardiac and vascular risks in a real-world setting. Methods: This pharmacovigilance study extracted records between January 2015 and December 2019 from the FDA Adverse Event Reporting System (FAERS) database. The association of seven PPI medications with cardiac and vascular events (CVEs) were evaluated. Two established pharmacovigilance methods, reporting odds ratio (ROR) and information components (IC) based statistical shrinkage, were used to measure disproportionality. Results: In total 62,140 CVE records associated with PPI use were investigated. Women showed a higher proportion (54.37%) of PPI-associated CVEs. The median time from PPI initiation to CVE onset was 97 [interquartile range (IQR): 8-491] days, with the shortest median time of 42 days (IQR: 2-277 days) for esomeprazole, and the longest time of 389 days (IQR: 0-525 days) for dexlansoprazole. Although PPIs were not associated with elevated CVE risks compared those of the whole database (IC025/ROR025 = -0.39/0.74), various signals emerged. Despite some similarities exist between the PPIs, their cardiac and vascular safety profiles varied significantly. Pantoprazole showed the broadest spectrum of signals, from thrombotic thrombocytopenic purpura (IC025/ROR025 = 0.01/1.08) to renal haemangioma (IC025/ROR025 = 3.14/9.58). Esomeprazole showed the second-broadest spectrum of toxicities, ranging from duodenal ulcer hemorrhage (IC025/ROR025 = 0.07/1.28) to hypertensive nephropathy (IC025/ROR025 = 4.09/18.72). Vascular signals were more dominant than cardiac signals, suggesting that vascular function was more heavily affected. Hypertensive nephropathy, renal haemangioma, renal artery stenosis, and renal infarct had strong signals across most PPI regimens and merited further attention. Conclusions: PPIs may inflict various CVEs, particularly those involving the vascular system, on the users. Given the wide range of onset times and different toxicity profiles for various PPI medications, they should be prescribed with caution.

Renal toxicities in immune checkpoint inhibitors with or without chemotherapy: An observational, retrospective, pharmacovigilance study leveraging US FARES database.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have elicited durable antitumor responses in multiple types of cancers. However, ICIs could also induce potential toxicities that involve all organs, including renal system. In this study, we aimed to conduct a comprehensive description of the ICIs-induced renal toxicities and the potential effects of chemotherapy. METHODS: We conducted a pharmacovigilance study based on US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database between 01 January 2014 and 30 June 2019. Disproportionality analysis was used to assess the association between ICIs and renal adverse events (AEs), including reporting odds ratio (ROR) and information component (IC). ROR025 and IC025 are, respectively, 95% confidence interval lower end of ROR and IC. If the value of ROR025 exceeding one or IC025 higher than zero, then a signal was considered statistically significant. RESULTS: A total of 30,602,758 reports were extracted from the database, with 4578 reports for ICIs-associated renal AEs. Renal AEs were more frequently reported in anti-PD-1/PD-L1 versus anti-CTLA-4 monotherapy group (ROR: 1.75, 95% CI: 1.52-2.01). Similarly, renal AEs were more commonly reported in ICIs polytherapy other than monotherapy group (ROR: 1.18, 95% CI: 1.10-1.27). Notably, ICIs plus chemotherapy strategies reported more renal toxicities compared to sole ICIs regimens (ROR: 1.30, 95% CI: 1.17-1.45), whereas exhibited lower fatality outcome rates. Importantly, acute kidney injury (1139, 24.88%) and renal failure (464, 10.14%) were the top two most commonly reported ICIs-associated renal AEs, and also observed with the top two highest level of fatality outcome rates. CONCLUSIONS: A spectrum of renal AEs was detected in ICIs regimens and could be reinforced by ICIs combination. Compared to sole ICIs regimens, ICIs plus chemotherapy strategy reported more renal toxicities but lower fatality outcome rates. With the increasing popularity of ICIs especially combination strategies, it is vital important for clinicians to guarantee balance between durable clinical effects and potential renal toxicities in latest immunotherapy strategies.

Cardiovascular Toxicity of Carfilzomib: The Real-World Evidence Based on the Adverse Event Reporting System Database of the FDA, the United States.

Background: Carfilzomib, an effective proteasome inhibitor agent for the therapy of relapsed and refractory multiple myeloma, has been related to a significant number of cardiovascular events. However, patterns of cardiovascular complications associated with this agent remain poorly characterized in real-world settings. Objective: To gain further insight into the frequency, spectrum, clinical features, timing, and outcomes of carfilzomib-related cardiovascular toxicities. Methods: This disproportionality (case/non-case) study was conducted leveraging records from FAERS database from 2014 to 2019. Cardiovascular events were defined and broadly categorized eight entities using narrow version of the Standardized MedDRA Queries (SMQs). Reporting odds ratios (ROR) and information component (IC) were calculated to measure disproportionality. Additionally, statistical shrinkage was applied to reduce false-positive signals. Results: The final number of records involved was 28,479,963, with 3,370 records submitted for carfilzomib related cardiovascular events. Significant disproportionality association between carfilzomib administration and cardiovascular events was captured (IC025/ROR025 = 0.85/1.95) when exploring in the entire database. Upon further analysis, all eight broad categories of cardiovascular toxicities were disproportionately associated with carfilzomib with varying frequencies, time-to-onset, and severities. Cardiomyopathy-related complications (N = 1,301, 38.61%), embolic and thrombotic events (N = 821, 24.36%), and cardiac failure (N = 765, 22.70%) largely comprised the reported problems. Notably, the strongest signal was detected for cardiac failure (IC025/ROR025 = 1.33/2.59), followed by pulmonary hypertension (IC025/ROR025 = 1.19/2.34). Median onset time of cardiovascular events was 41days (Q1-Q3: 9-114 days), with the shortest median time being 16 days (Q1-Q3: 4-85 days) for ischemic heart disease, with the longest time being 68 days (Q1-Q3: 21-139 days) for embolic and thrombotic events. Torsade de pointes/QT prolongation was identified as a new complication (IC025/ROR025 = 0.33/1.29) and was particularly noteworthy for highest death proportion (44.11%). Conclusions: Treatment with carfilzomib can lead to severe and versatile cardiovascular events. Early and intensive monitoring is important, particularly in the first 3 months after carfilzomib initiation. Maximizing the benefit while reducing potential cardiovascular harms of carfilzomib should become a priority.

Safety of SGLT2 Inhibitors: A Pharmacovigilance Study from 2013 to 2021 Based on FAERS.

Background: Sodium-glucose co-transporter-2 inhibitors (SGLT2is) are widely used in clinical practice for their demonstrated cardiorenal benefits, but multiple adverse events (AEs) have been reported. We aimed to describe the distribution of SGLT2i-related AEs in different systems and identify important medical event (IME) signals for SGLT2i. Methods: Data from the first quarter (Q1) of 2013-2021 Q2 in FAERS were selected to conduct disproportionality analysis. The definition of AEs and IMEs relied on the system organ classes (SOCs) and preferred terms (PTs) by the Medical Dictionary for Regulatory Activities (MedDRA-version 24.0). Two signal indicators, the reported odds ratio (ROR) and information component (IC), were used to estimate the association between SGLT2is and IMEs. Results: A total of 57,818 records related to SGLT2i, with 22,537 SGLT2i-IME pairs. Most SGLT2i-related IMEs occurred in monotherapy (N = 21,408, 94.99%). Significant signals emerged at the following SOCs: "metabolism and nutrition disorders" (N = 9,103; IC025 = 4.26), "renal and urinary disorders" (3886; 1.20), "infections and infestations" (3457; 0.85). The common strong signals were observed in diabetic ketoacidosis, ketoacidosis, euglycaemic diabetic ketoacidosis and Fournier's gangrene. Unexpected safety signals such as cellulitis, osteomyelitis, cerebral infarction and nephrolithiasis were detected. Conclusion: Our pharmacovigilance analysis showed that a high frequency was reported for IMEs triggered by SGLT2i monotherapy. Different SGLT2is caused different types and the association strengths of IMEs, while they also shared some specific PTs. Most of the results are generally consistent with previous studies, and more pharmacoepidemiological studies are needed to validate for unexpected AEs. Based on risk-benefit considerations, clinicians should be well informed about important medical events that may be aggravated by SGLT2is.

Metabolic and Nutritional Disorders Following the Administration of Immune Checkpoint Inhibitors: A Pharmacovigilance Study.

Background: Although several metabolic and nutritional disorders (MNDs) have been reported in the recipients of immune checkpoint inhibitors (ICIs), these events have not been fully captured and comprehensively characterized in real-world population. Objectives: To provide complete metabolic and nutritional toxicity profiles after ICIs (single and combined) initiation through an integrated big database. Methods: Reporting odds ratios (ROR) and information component (IC) based on statistical shrinkage transformation were utilized to perform disproportionality analysis using the US Food and Drug Administration Adverse Events Reporting System. Both ROR and IC were used to calculate disproportionality when compared with the whole database, but only ROR was used when comparison was made for different ICI strategies. Only when both the lower limits of 95% confidence intervals (CIs) for ROR (ROR025) and IC (IC025) exceeded specified threshold values (1 and 0, respectively) was regarded as a signal. Results: A total of 29,294,335 records were involved and 8,662 records were for MNDs in patients exposed to ICIs. Statistically significant association was detected between ICIs use and total MNDs (IC025/ROR025 = 1.06/2.19). For monotherapy, three ICI monotherapies (anti-PD-1, anti-PDL-1, and anti-CTLA-4) were all disproportionately associated with MNDs. Statistically significant differences in reporting frequencies also emerged when comparing anti-PD-1 with anti-PD-L1/anti-CTLA-4 monotherapy, with RORs of 1.11 (95%CI 1.01-1.21), and 1.35 (95%CI 1.23-1.48), respectively. Notably, combination therapy was associated with a higher reporting frequency of theses toxicities compared to monotherapy with a ROR of 1.56 (95%CI 1.48-1.64). Additionally, disproportionality analysis at High-level Group Term level highlighted eight broad entities of MNDs. Further disproportionality analysis at Preferred Term level indicated a wide range and varied strength of signals. For ICI monotherapy, nivolumab and pembrolizumab showed the broadest spectrum of MNDs. For combination therapy, a variety of signals were detected for nivolumab + ipilimumab therapy even comparable to two PD-1 monotherapies. Conclusion: Metabolic and nutritional complications could be provoked by ICI monotherapy (especially anti-PD-1) and further reinforced by combination therapy. Clinicians and patients should be informed about these potential risks that might be encountered in real-world practice. Aforehand education and regular monitoring of related biochemical parameters (calcium, sodium, potassium, protein) are recommended to ensure better cancer survivorship.

Dynamic statistical model for predicting the risk of death among older Chinese people, using longitudinal repeated measures of the frailty index: a prospective cohort study.

BACKGROUND: Frailty is a common characteristic of older people with the ageing process. We aimed to develop and validate a dynamic statistical prediction model to calculate the risk of death in people aged ≥65 years, using a longitudinal frailty index (FI). METHODS: One training dataset and three validation datasets from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) were used in our study. The training dataset and validation datasets 1 to 3 included data from 9,748, 7,459, 9,093 and 6,368 individuals, respectively. We used 35 health deficits to construct the FI and a longitudinal FI based on repeated measurement of FI at every wave of the CLHLS. A joint model was used to build a dynamic prediction model considering both baseline covariates and the longitudinal FI. Areas under time-dependent receiver operating characteristic curves (AUCs) and calibration curves were employed to assess the predictive performance of the model. RESULTS: A linear mixed-effects model used time, sex, residence (city, town, or rural), living alone, smoking and alcohol consumption to calculate a subject-specific longitudinal FI. The dynamic prediction model was built using the longitudinal FI, age, residence, sex and an FI-age interaction term. The AUCs ranged from 0.64 to 0.84, and both the AUCs and the calibration curves showed good predictive ability. CONCLUSIONS: We developed a dynamic prediction model that was able to update predictions of the risk of death as updated measurements of FI became available. This model could be used to estimate the risk of death in individuals aged >65 years.

Hematological toxicities in immune checkpoint inhibitors: A pharmacovigilance study from 2014 to 2019.

Immune checkpoint inhibitors (ICIs) have shown remarkable clinical effects in many cancer types. However, ICIs could also induce severe organ system toxicities, including those of the hematological system. The present study aimed to extensively characterize the hematological toxicities of ICIs immunotherapy. Data were extracted from the US Food and Drug Administration Adverse Event Reporting System (FAERS) database from January 1, 2014, to March 31, 2019. Disproportionality analysis, including information component (IC) and reporting odds ratio (ROR), was used to detect potential disproportionality signal. The lower boundary of the 95% confidence interval of IC (IC025 ) exceeding zero or that of ROR (ROR025 ) exceeding one was considered statistically significant for detecting disproportionality signal. A total of 29 294 335 records were extracted from the database, with 132 573 related to ICIs. Overall, hematological adverse events (AEs) were more frequently reported in ICIs (IC025 : 0.81; ROR025 : 1.80). On further analysis, hematological AEs were overreported in female patients (female vs male, ROR025 : 1.04) and anti-CTLA-4 monotherapy groups (anti-CTLA-4 vs anti-PD-1, ROR025 : 1.33) and polytherapy groups (polytherapy vs monotherapy, ROR: 1.20, ROR025 : 1.11). Moreover, class-specific hematological AEs were also detected and differed in unique ICI regimens. Notably, disseminated intravascular coagulation had the highest proportion of death outcomes among the top 10 most frequently reported ICI-associated hematological AEs. Our study shows a high reporting frequency of hematological AEs induced by ICI monotherapy (especially by anti-CTLA-4 therapy) and reinforced by polytherapy. A spectrum of class-specific disproportionality signal was also detected; some were fatal and reported for the first time. The heterogeneous clinical spectrum of hematological toxicities, including the non-negligible proportion of death as reported outcome, are warranted to be reminded by clinicians. Early recognition and management of ICI-related hematological AEs are highly important and further studies are needed to confirm the results of our study.

Ear and labyrinth toxicities induced by immune checkpoint inhibitors: a disproportionality analysis from 2014 to 2019.

Aim: We aimed to systematically characterize ear and labyrinth toxicities after immune checkpoint inhibitors (ICIs) initiation. Materials & methods: Data were extracted from the US FDA Adverse Event Reporting System database. Disproportionality analysis including information component and reporting odds ratio (ROR) was performed to access potential signals. Results: In FDA Adverse Event Reporting System database, 284 records for ICIs-associated ear/labyrinth adverse events (AEs) were involved. In general, there was no significant association between total ICIs use and total ear and labyrinth AEs (ROR025: 0.576). However, in ICIs monotherapy and polytherapy groups, signals were detected in several specific ear and labyrinth AEs. Conclusion: Total ear and labyrinth toxicities were not significantly reported with ICI immunotherapy, while class-specific ear toxicities were detected in some strategies.

Endocrine toxicity of immune checkpoint inhibitors: a real-world study leveraging US Food and Drug Administration adverse events reporting system.

BACKGROUND: Immune-checkpoint inhibitors (ICIs) emerged as a novel class of drugs for the treatment of a broad spectrum of malignancies. ICIs can produce durable antitumor responses but they are also associated with immune-related adverse events (irAEs). Endocrinopathies have reported as one of the most common irAEs of ICIs. METHODS: This study aimed to quantify association of endocrine adverse events (AEs) and ICI therapy and also to characterize the profiles of ICI-related endocrine complications from real-world practice. Data from the first quarter of 2014 to first quarter of 2019 in FDA Adverse Event Reporting System (FAERS) database were gathered to conduct disproportionality analysis. The definition of endocrine AEs relied on the preferred terms (PTs) provided by the Medical Dictionary for Regulatory Activities (MedDRA). Two signal indices based on statistical shrinkage transformation, reporting odds ratios (ROR) and information component (IC), were used to evaluate correlations between ICIs and endocrine events. For ROR, it was defined a signal if the lower limit of the 95% confidence interval (ROR025) more than one, with at least 3 cases. For IC, lower end of the 95% confidence interval of IC (IC025) exceeding zero was deemed statistically significant. RESULTS: A total of 29,294,336 records were involved, among these 6260 records related to endocrine AEs after ICIs treatment were identified. In general, male had a slightly lower reporting frequencies for ICIs-related endocrinopathies compared with female but not significant (ROR = 0.98 95%CI: 0.93-1.04) and the difference varied in several common endocrine AEs. Notably, in general, ICI drugs were significantly associated with over-reporting frequencies of endocrine complications, corresponding to IC025 = 2.49 and ROR025 = 5.99. For monotherapy, three strategies (anti-PD-1, anti-PD-L1 and anti-CTLA-4) were all associated with significant increasing endocrine events. Different reporting frequencies emerged when anti-CTLA-4 therapy was compared with anti-PD-1/PD-L1 medications for endocrine toxicities, corresponding to ROR = 1.68 (95%CI 1.55-1.83), ROR = 2.54 (95%CI 2.20-2.93), respectively. Combination therapy was associated with higher risk of endocrinopathies compared with monotherapy (ROR = 2.00, 95%CI 1.89-2.11). When further analysis, the spectrum of endocrine AEs differed in immunotherapy regimens. Hypothyroidism (N = 885,14.14%), adrenal insufficiency(N = 730,11.66%), hypophysitis (N = 688,10.99%) and hyperthyroidism (N = 472,7.54%) were top 4 ranked endocrine events after ICI therapy and their reporting frequency also differed in ICI immunotherapies. CONCLUSION: Our pharmacovigilance analysis shows a high reporting frequency of endocrine AEs provoked by ICI monotherapy (especially anti-CTLA-4 therapy) and further reinforced by combination therapy. In addition, treatment with different ICI immunotherapies may result in a unique and distinct profile of endocrinopathies. Early recognition and management of ICI-related endocrine irAEs is of vital importance in clinical practice.

Prevalence of Atrial Fibrillation in Hospital Encounters With End-Stage COPD on Home Oxygen: National Trends in the United States.

BACKGROUND: This study aimed to evaluate the prevalence of atrial fibrillation (AF) in hospital encounters with end-stage COPD on home oxygen admitted for COPD exacerbation. METHODS: We used the 2003 to 2014 Nationwide Inpatient Sample to conduct a retrospective analysis. This study included all patients ≥ 18 years of age with a primary diagnosis of COPD on home oxygen who were hospitalized for COPD exacerbation. We used multivariate-adjusted models to evaluate the association of AF with clinical factors, cost, length of stay, and hospital outcomes. RESULTS: In total, 1,345,270 patients were included; of these, 244,488 (18.2%) had AF. The AF prevalence increased from 12.9% in 2003 to 21.3% in 2014 (P < .0001) and varied by age, sex, race, income, insurance type, and hospital region. Advancing age, female sex, white race, high income, and large hospital size were associated with increased odds of AF. Presence of AF was a risk predictor for in-hospital death (OR, 1.54; 95% CI, 1.45-1.65), acute respiratory failure (OR, 1.09; 95% CI, 1.06-1.12), invasive mechanical ventilation (OR, 1.37; 95% CI, 1.29-1.47), noninvasive mechanical ventilation (OR, 1.14; 95% CI, 1.09-1.18), acute kidney injury (OR, 1.09; 95% CI, 1.04-1.13), sepsis (OR, 1.23; 95% CI, 1.10-1.37), and stroke (OR, 1.80; 95% CI, 1.40-2.32). AF was also associated with increased cost and length of stay. CONCLUSIONS: AF prevalence in hospital encounters with end-stage COPD increased from 2003 to 2014. Better management strategies for patients with end-stage COPD comorbid with AF are needed, especially in elderly individuals.