Global Cohort Research Articles

Higher number vasopressor usage linked to poorer outcomes despite obtaining hemodynamic goals in acute myocardial infarction complicated by cardiogenic shock

Abstract Introduction Despite using vasoactive drugs to achieve hemodynamic goals in AMI-CS, the outcome of patients that achieve these goals and its relation with the number of drugs is uncertain. Methods 309 AMI-CS+PAC patients, divided by vasoactives 0-1, 2, or >2. Repeated measures ANOVA was used to compare 24-h hemodynamic data. The primary outcome was in-hospital mortality, and univariate and multivariate analyses were performed, adjusting for age, sex, type of MI, SCAI, multiorgan failure (MOF), and type of reperfusion. We also examined patients who achieved hemodynamic goals and analyzed the high achievers(≥5 goals) based on: MAP, CI, CPI, RAP, PCWP, and PAPI. Results 57 had 0-1, 76 =2, and 176 >2 vasoactives. Most patients were male(82%) with a median age 61(53-67) and had STEMI(82.8%). No differences in age, diabetes, previous HF, MI, PCI, CABG, smoking history, OHCA, or type of AMI. Killip-Kimball was overall worse in 2 and >2 groups(P<0.001). LVEF decreased as drugs increased (>2=30, 2=35, 0-1=40%; P<0.001). Higher leucocyte count, Cr, AST, ALT, LDH, and lactate with lower platelets, eGFR, and pH were seen as the number of drugs increased. No differences in Hb, electrolytes, albumin, C-reactive protein, primary reperfusion, angiography, number of vessels, or revascularization were noted. The use of mechanical ventilation and hemodialysis was lower in the 0-1 group. SCAI, MODS, MOF, and AKI were higher in 2 and >2 group. Mortality was higher in the>2 group(67.6) compared to 2 (31.6) and 0-1 (12.3%; P<0.001). In the serial measures, CI (Fig1A), CPO, CPI (Fig1B), CPIRAP, SBP, MAP, and PAPI(Fig1D,C) had lower values in the >2 group compared with the 2 or 0-1(P<0.001), whereas higher RAP and PCWP were seen in the >2 group(P<0.001, 0.009, Fig1E,F). The number of vasoactives was an independent predictor of mortality, and the estimated probability of mortality was higher as the number of drugs increased, despite achieving hemodynamic goals(Fig1; blue= 0-1, green=2, red >2). In the global cohort, patients receiving 2 or more vasoactive drugs had an increased hazard ratio compared to those receiving 0-1 drugs (Fig2C-D). Among high hemodynamic goal achievers (n=115), a difference in the Kaplan-Meier analysis was observed when compared with the 0-1 group, but no difference was seen with 2 drugs(HR 2.31[0.55-9.7; 0.252], HRadj 2.12[0.43-10.46; 0.358]). However, differences were observed when >2 drugs were used(HR 6.85[3.57-22.51; 0.002] and HRadj 7.38[1.96-27.77; 0.003])(Fig2B). In addition, a comparison of each variable subgroup achiever showed differences between the 0-1 and >2 vasoactives even after adjustment. In contrast, when compared vs 2 vasoactives, only CI, CPI, CPIRAP, and PAPI retained significance after adjustment(Fig2C-D). Conclusion Despite achieving hemodynamic goals in AMI-CS, the use of more vasoactive drugs may result in poorer outcomes. Furthermore, investigating strategies to reduce vasoactives, such as upfront MCS is warranted.Fig 1.Blue=0-1 Green=2 Red=>2 vasoactiveFig 2.

Oral anticoagulant use and outcomes in Asian patients with atrial fibrillation in the GLORIA-AF Registry

Abstract Background Ethnic differences in the management and outcomes of patients with atrial fibrillation (AF) have been shown in previous studies, but available data is still limited, although urgently needed. Purpose to analyse oral anticoagulant (OAC) prescription, OAC discontinuation, and long-term risk of major outcomes in Asian patients with AF, using data from a global prospective cohort study. Methods Using data from the GLORIA-AF Registry Phase II and III, we analysed patients according to their self-reported ethnicity (Asian vs. Non-Asian), and according to Asian ethnic subgroup (i.e. Chinese, Japanese, Korean and other Asian). Odds of OAC prescription were analysed through multivariable logistic regression, while the risk of OAC discontinuation and adverse outcomes were analysed through multivariable Cox-regression model. Primary outcome of this analysis was defined as the composite of all-cause death and major adverse cardiovascular events (MACE). Results 34,421 AF patients were included (70.0±10.5 years, 45.1% females, 6,900 (20.0%) Asian). Compared to Non-Asian subjects, prescription of OAC and non-vitamin K antagonist oral anticoagulant (NOAC) was lower in Asian subjects (Odds Ratio [OR] and 95% Confidence Intervals (CI): 0.23 [0.22-0.25] and 0.66 [0.61-0.71], respectively; Figure 1), but higher in the Japanese subgroup. Asian ethnicity was also associated with OAC discontinuation (Hazard Ratio [HR] and [95%CI]: 1.79 [1.67-1.92]), and lower risk of the primary composite outcome (HR [95%CI]: 0.86 [0.76-0.96]; Figure 2). Among the secondary outcomes, Asian patients had also higher risk of thromboembolism and intracranial haemorrhage, and lower risk of major bleeding events. Conclusions In this large, contemporary cohort of patients with AF, Asian subjects received suboptimal management of thromboembolic risk, and showed a peculiar long-term risk of adverse outcomes. Integrated and appropriate treatment of these patients is crucial to improve their prognosis.Figure 1Figure 2

Results of atypical flutter ablation in the era of high density electroanatomical mapping (the RAFAELA study)

Abstract Introduction Atypical flutter (AFL) ablation is a technically challenging procedure with limited long-term efficacy according to prior studies and not exempt from risks. Purpose The aim of this study was to describe the efficacy, in terms of acute and long-term rhythm management, and safety of AFL ablation guided by high-density electroanatomical mapping in a population of contemporary patients. We aimed also to compare results between different patient populations. Methods From june 2015 to November 2021, all consecutive AFL ablation procedures guided by high-density electroanatomical mapping were included in the study. Patients were classified in 4 groups according to history of atrial catheter ablation, cardiac surgery, congenital heart disease or none of the above (considered as primary disease). Activation and voltage mapping were used to define AFL circuits and substrate. After AFL characterization, radiofrequency lesions were performed to operator’s discretion until AFL termination. Programmed atrial stimulation was repeated to test AFL inducibility, and any sustained induced atrial arrhythmia was ablated. Procedural success was defined as termination of every induced AFL and no-inducibility. A 3-month blanking period was considered. Follow-up included visits with ECG and/or 24h Holter-ECG at 3, 6, 12, 24 months, and from there on according to physician’s discretion. Results 190 AFL procedures in 160 patients were included. Patient and procedural characteristics of the global cohort as well as different patient populations (27% primary, 37.9% post-ablation, 15.3% post-surgery, 20% congenital heart disease (CHD)) can be found in figure 1 (table). Survival free from atrial arrhythmias in pre-specified groups is shown in figure 2 (left). Overall, a 2-year ∼50% recurrence rate was observed, with a tendency to better outcome in patients with congenital heart disease (∼70%), over the rest of the groups, which behaved similarly (p=0.281). Progression to permanent atrial arrhythmia was lower in this subgroup (2.7% vs 23.5%, p=0.028), as shown in figure 2 (right), probably related to higher rhythm control efforts and stricter follow-ups. CONCLUSIONS In the era of high-density electroanatomical mapping, acute procedural success is achievable in the majority of patients, but recurrence rate remains high, with an approximate 50% 2-year recurrence rate except for congenital heart disease patients, which tend to show better survival free from atrial arrhythmias.Figure 1Figure 2

Soluble ST2 biomarker utility in the comprehension of the clinical course of atrial fibrillation

Abstract Background Atrial fibrillation (AF) is the more frequent arrhythmia in clinical practice and probably one of the more analyzed. Despite this, the clinical pattern classification not always correlates with the clinical course of AF. There are still a lack of biomarkers to predict recurrence and the clinical course of this disease. Purpose ST2 soluble (ST2S) biomarker has being previously analyzed by our group in patients with AF and electrical cardioversion (ECV) demonstrating utility to predict recurrence. We sought to analyze the clinical outcome of patients with AF who underwent an ECV or pulmonary vein isolation (PVI) and its correlation with the ST2S biomarker at mid-term follow-up. Methods We performed a prospective, observational clinical trial that included 250 patients with AF who were referred to our hospital for a clinical procedure including ECV or PVI from September 2016 to 2019. A total of 40 matched controlled patients were also included for the initial analysis. ST2S was analyzed from blood samples at baseline, 3- and 6-months follow-up. Results From 250 patients with AF: 94 underwent an ECV and 156 patients an PVI. Mean age was of 58.5 ±10.4 years. From the 156 PVI: 68 had paroxysmal and 88 persistent AF. Clinical follow-up was continued for 1 year and recurrence was of 65.9% in ECV and 22.4% in PVI patients. Clinical and echocardiographic characteristic are described in table1. The initial value of the ST2S biomarker was higher in AF cases with respect to controls (p<0.001). The patients with paroxysmal AF had higher levels of ST2S.0 (12113.4 pg/mL) respect to control cases but with no significant difference (p=0.234). Comparing the values of ST2S in persistent AF patients (15634.8 pg/mL) with controls the value was higher with a significant difference. ST2S baseline values were compared according to the rhythm and patients in AF had significantly higher levels with respect to those in sinus rhythm (SR). ST2S baseline values were also compared according to heart rate (HR) and those in tachycardia had higher levels respect to those who didn't(Table2). When analyzing ST2S levels in the complete cohort of patients with AF according to recurrence, there were no significant differences (Figure1). In multivariant analysis only AF rhythm and LA index volume were significant predictors of recurrence at 3 months follow-up and AF rhythm and age were predictors at 6 months follow-up. Conclusions ST2S baseline values were higher in persistent AF with respect to paroxysmal AF and only persistent AF patients had higher levels compared with controls. Initial ST2S biomarker levels did not have a predictive value in the global cohort of AF but do correlate with the type of AF and AF rhythm. With these results we consider that even though there is an association with AF and ST2S biomarker levels, when analyzing independently to the type of procedure ST2S values were not predictive of recurrence at mid-term follow-up.

Impact of chronic obstructive pulmonary disease on the natural history of atrial fibrillation: a report from the GLORIA-AF registry phase II & III

Abstract Background The relationship between chronic obstructive pulmonary disease (COPD) and atrial fibrillation (AF) remains unclear. COPD may influence the management and prognosis of AF and may affect treatments, including beta-blockers prescription. Purpose To investigate the association between COPD and AF, and assess the impact of COPD on treatment patterns and major adverse outcomes in a large contemporary global cohort of AF patients. Methods The GLORIA-AF Registry enrolled newly diagnosed AF patients with at least 1 stroke risk factor. Diagnosis of COPD and treatments (including oral anticoagulant [OAC]) prescribed were recorded by investigators at baseline. We evaluated clinical characteristics associated with the diagnosis of COPD at baseline, OAC and other treatment prescription, and risk of OAC discontinuation. Adjusted Cox-regression models were utilized to analyse the relationship of COPD with major outcomes including a primary composite outcome of all-cause death and major adverse cardiovascular events (MACE). Results 36,263 patients (mean age 70.1±10.5 years, 45.3% females) were included in this analysis. Patients with COPD (n=2,261, 6.2%) were older, and had higher thromboembolic risk. Increasing age, smoking status, BMI and cardiovascular comorbidities were associated with higher odds of COPD diagnosis at baseline. COPD was associated with higher odds of receiving OACs (Odds Ratio [OR] and 95% Confidence Interval [CI]: 1.31, 1.15-1.49), and with a higher risk of discontinuing OACs during follow-up (hazard ratio (HR): 1.14, 95%CI: 1.03-1.27). COPD patients were more likely prescribed with digoxin and verapamil or diltiazem, with lower prescription of beta-blockers (OR [95%CI]: 0.79, 0.72-0.87; Figure 1) and amiodarone (OR [95%CI]: 0.83, 0.73-0.96). Patients with COPD were at higher risk of the primary outcome of all-cause death and MACE (Hazard Ratio [95%CI]: 1.78, 1.58-2.01; Figure 2), and were also found at higher risk of all-cause mortality, cardiovascular death, MACE and major bleeding, while no statistically significant differences were observed for thromboembolism. There was no statistically significant interaction between beta-blocker use and risk of the primary composite outcome in COPD patients. Conclusions COPD is associated with different treatment patterns in AF patients, higher risk of OAC discontinuation, and ultimately a poorer clinical prognosis, with an increased risk of all-cause death, MACE and major bleeding. Beta-blocker use appeared safe in COPD patients.Figure 1Figure 2

Novel Causal Inference Method Estimates Treatment Effects of Contemporary Drugs in a Global Cohort of Patients with Relapsed and Refractory Mature T-Cell and NK-Cell Neoplasms

There is no universal approach to treat patients with relapsed and refractory (RR) mature T-cell and NK-cell neoplasms (TNKL). While participation in a clinical trial is favored, appropriate options are often unavailable. Thus, outside of a trial, physicians may rely on real world evidence when making a treatment choice. We hypothesized that innovative causal predictive models that utilize existing clinical information could estimate comparative efficacy of various treatments and support clinical decision making. As the first step, we built a large global cohort of 925 patients with RR TNKL diagnosed between Jan 2010 and Dec 2020 representing 9 countries. Eligible patients received either a single agent (SA) such as an epigenetic modifier, small molecule inhibitor, brentuximab vedotin (BV) among others, or platinum-, gemcitabine-, ifosfamide-based cytotoxic chemotherapy (CC) in the second line setting. Patients were followed from lymphoma diagnosis, or first retreatment start date to death or lost to follow-up. Thirteen covariates [relapsed/refractory state, with refractory defined as lack of complete remission (CR) to first line therapy, country Japan, age >50 years, histological subtype AITL, IPI, PIT score, response to 1 st line treatment, 2 nd line treatment (SA or CC), response to 2 nd line treatment, autologous stem cell transplantation (Auto-SCT), response to ASCT, allogeneic stem cell transplantation (Allo-SCT), response to Allo-SCT] were identified to have an independent prognostic effect on overall survival (OS). Based on measures of Brier score (BS) and Concordance index (CI), eight of them were selected for multivariate Cox regression model. We observed comparable performance of the Cox models utilizing these 8 covariates (CI: 0.755; BS:0.174) versus 5 of these 8 covariates (CI:0.744; BS:0.186). Hence 5 covariates were utilized for further OS analyses. We found that multivariate Cox outperforms other traditional models including random survival forest and gradient boosted (Table 1). Since data under consideration is observational and not derived from a clinical trial, there may be several (unobserved) confounders leading to bias in the outcomes, which are not adjusted for by these traditional approaches. We introduce a novel causal method, Synthetic Intervention (SI), which adjusts for such biases. For comparative evaluation of SI with multivariate Cox, due to data requirement for SI, we chose only two covariates [response to 1 st line stratified as CR, partial remission (PR), stable disease (SD) and progressive disease (PD) and administration of second line treatment (SA or CC)] (Table 1). We found that SI outperforms multivariate Cox. Further, despite heterogeneity in OS across the 8 cohorts, the median OS prediction of SI was comparable to actual median OS for each cohort, thus highlighting robustness of SI (Figure 1). All the performance evaluations were done using 60:40 train: test split, repeated 500 times. We confirmed previous reports that relapsed patients had superior OS compared to primary refractory patients across common histologies: PTCL-NOS (p<.0001), AITL (p=.036), ENKTCL (p=.027), and ALK- ALCL (p=.001). Those who received SA at first retreatment had superior OS compared to those treated with CC in AITL (p<.0005) and ALK- ALCL (p=.036) and comparable OS in PTCL-NOS, ENKTCL, and ALK+ ALCL. In ALK- ALCL, those treated with BV had superior OS compared to CC (p=.027). Patients with AITL treated with small molecule inhibitors (SMI) had greater OS compared to those treated with CC (p<.0005) and epigenetic modifiers (EM) (p=.001), with the most common SMIs including alisertib, duvelusib, cerdulatinib, and cyclosporine. Those who responded to EM and BV (CR+PR+SD) had superior OS compared to non-responders (PD) in PTCL-NOS (p=.004) and ALK- ALCL (p<0.0005). Among patients who underwent SCT after second line therapy, those bridged with SA had comparable OS to CC in PTCL-NOS and an improved trend (p=.073) in AITL. In summary, we have characterized the largest global cohort of RR patients with TNKL in the era of contemporary therapies. As a causal analysis method, SI demonstrates the causal effect superiority of SA over CC in terms of survival outcomes for patients who responded differently to their 1st line treatment. Moreover, it achieves prediction accuracy comparable to, if not better than, Cox regressions, one of the most widely used methods in survival analysis.

Long-term outcomes of the global tuberculosis and COVID-19 co-infection cohort.

Longitudinal cohort data of patients with tuberculosis (TB) and coronavirus disease 2019 (COVID-19) are lacking. In our global study, we describe long-term outcomes of patients affected by TB and COVID-19. We collected data from 174 centres in 31 countries on all patients affected by COVID-19 and TB between 1 March 2020 and 30 September 2022. Patients were followed-up until cure, death or end of cohort time. All patients had TB and COVID-19; for analysis purposes, deaths were attributed to TB, COVID-19 or both. Survival analysis was performed using Cox proportional risk-regression models, and the log-rank test was used to compare survival and mortality attributed to TB, COVID-19 or both. Overall, 788 patients with COVID-19 and TB (active or sequelae) were recruited from 31 countries, and 10.8% (n=85) died during the observation period. Survival was significantly lower among patients whose death was attributed to TB and COVID-19 versus those dying because of either TB or COVID-19 alone (p<0.001). Significant adjusted risk factors for TB mortality were higher age (hazard ratio (HR) 1.05, 95% CI 1.03-1.07), HIV infection (HR 2.29, 95% CI 1.02-5.16) and invasive ventilation (HR 4.28, 95% CI 2.34-7.83). For COVID-19 mortality, the adjusted risks were higher age (HR 1.03, 95% CI 1.02-1.04), male sex (HR 2.21, 95% CI 1.24-3.91), oxygen requirement (HR 7.93, 95% CI 3.44-18.26) and invasive ventilation (HR 2.19, 95% CI 1.36-3.53). In our global cohort, death was the outcome in >10% of patients with TB and COVID-19. A range of demographic and clinical predictors are associated with adverse outcomes.

Socioeconomic Factors Predict Long-Term Quality of Life of Cancer Survivors: An International Survey

IntroductionDespite advances in cancer treatment, the quality of life (QOL) of survivors varies significantly. We assessed the correlation between socioeconomic factors and long-term QOL in a global cohort of cancer survivors. Materials and methodsPatients were offered surveys via online support groups. Using the Short Form-12 validated questionnaire, physical QOL (PQOL) and mental QOL (MQOL) well-being were compared to the general population. Socioeconomic factors were assessed with regression analysis for impact on QOL. ResultsSeven hundred eighty two survivors from six continents responded. They were 57 ± 13 y and 68% female, 90.8% White, with 43 distinct cancer diagnoses. All survivors had PQOL and MQOL scores lower than the general population. Lower education level, household income, and non-White race all correlated with reduced PQOL and/or MQOL. Age was negatively correlated with PQOL (r = −0.08, P = 0.03) and positively correlated with MQOL (r = 0.142, P < 0.001). Care at large regional/academic centers was associated with higher MQOL (42 ± 14 versus 38 ± 11, P = 0.005). Age (β = −0.1, P = 0.04), education (β = 1.1, P = 0.005), and income (β = 2.0, P < 0.001) were predictors of PQOL, while age (β = 0.2, P < 0.001), income (β = 1.7, P = 0.002), and community hospital care (β = −3.6, P = 0.013) were predictors of MQOL. ConclusionsIn a large international survey of cancer survivors, we identified socioeconomic factors and their associations with QOL. Further work should be directed to provide durable support across all socioeconomic classes.

Are interleukin 17 and interleukin 23 inhibitors associated with malignancies?-Insights from an international population-based study.

Cancer risk after long-term exposure to interleukin (IL)-23 inhibitors (IL-23i) and IL-17 inhibitors (IL-17i) remains to be delineated. To evaluate the risk of malignancies in patients with psoriasis treated with IL-23i and IL-17i relative to those prescribed tumour necrosis factor inhibitors (TNFi) during the first 5 years following drug initiation. A global population-based cohort study included two distinct analyses comparing patients with psoriasis under different therapeutic modalities; (i) new users of IL-17i(n = 15,331) versus TNFi (n = 15,331) and (ii) new users of IL-23i (n = 5832) versus TNFi (n = 5832). Patients prescribed IL-17i experienced a decreased risk of non-Hodgkin lymphoma (NHL; HR, 0.58; 95% CI, 0.40-0.82; p = 0.002), colorectal cancer (HR, 0.68; 95% CI, 0.49-0.95; p = 0.024), hepatobiliary cancer (HR, 0.68; 95% CI, 0.58-0.80; p < 0.001), ovary cancer (HR, 0.48; 95% CI, 0.29-0.81; p = 0.005), melanoma (HR, 0.52; 95% CI, 0.37-0.73; p < 0.001), and basal cell carcinoma (BCC; HR, 0.57; 95% CI, 0.48-0.67; p < 0.001). IL-23i was associated with a reduced risk of NHL (HR, 0.39; 95% CI, 0.19-0.78; p = 0.006), hepatobiliary cancer (HR, 0.44; 95% CI, 0.31-0.62; p < 0.001) and BCC (HR, 0.76; 95% CI, 0.57-0.99; p = 0.046). In a sensitivity analysis comparing patients managed by IL-17i and IL-23i with their biologic-naïve counterparts, these classes were associated with decreased risk of several malignancies. IL-17i and IL-23i are associated with decreased risk of several malignancies. These findings should be considered prior to the prescription of biologics.

Generation Z's perceptions of a good life beyond consumerism: Insights from the United States and Finland

AbstractThis paper examines Generation Z consumers' perceptions of a good life beyond consumerism and how their perceptions and practices have evolved during crises and the cultural context in which they live. We present a unique theoretical and empirical cross‐cultural investigation which focuses on the ecological crisis and COVID‐19 pandemic, and the changes they have caused to Gen Zs' daily lives in the United States (California) and Finland. Two large qualitative data sets were collected through focus group interviews and open‐ and closed‐ended surveys before and during COVID‐19 and analyzed via the PERMA framework. Findings revealed that Gen Zs' pathways that lead to a good life include: healthy behaviors and balance; positive and meaningful relationships; happiness and positivity; meaningful things; productivity and goals; and daily routines. Findings also indicated that since COVID‐19, Gen Zs are increasingly shifting toward virtuous behaviors and eudaimonic‐oriented life, in which moderation, meaningfulness, and self‐realization play key roles. Gen Zs are characterized as a global consumer cohort and a driver of change for a sustainable future, thus understanding how these future professionals, leaders, and mainstream consumers perceive a good life provides theoretical and practical insights into how to provide ecologically sustainable well‐being for nature and future generations.

S481 Deciphering the Intersection of Celiac Disease and Eosinophilic Esophagitis in Pediatric and Adult Patients: Insights From a Global Cohort

S481 Deciphering the Intersection of Celiac Disease and Eosinophilic Esophagitis in Pediatric and Adult Patients: Insights From a Global Cohort

Predictors of Functional Impairment in Bipolar Disorder: Results From 13 Cohorts From Seven Countries by the Global Bipolar Cohort Collaborative.

Persistent functional impairment is common in bipolar disorder (BD) and is influenced by a number of demographic, clinical, and cognitive features. The goal of this project was to estimate and compare the influence of key factors on community function in multiple cohorts of well-characterized samples of individuals with BD. Thirteen cohorts from 7 countries included n = 5882 individuals with BD across multiple sites. The statistical approach consisted of a systematic uniform application of analyses across sites. Each site performed a logistic regression analysis with empirically derived "higher versus lower function" as the dependent variable and selected clinical and demographic variables as predictors. We found high rates of functional impairment, ranging from 41 to 75%. Lower community functioning was associated with depressive symptoms in 10 of 12 of the cohorts that included this variable in the analysis. Lower levels of education, a greater number of prior mood episodes, the presence of a comorbid substance use disorder, and a greater total number of psychotropic medications were also associated with low functioning. The bipolar clinical research community is poised to work together to characterize the multi-dimensional contributors to impairment and address the barriers that impede patients' complete recovery. We must also identify the core features which enable many to thrive and live successfully with BD. A large-scale, worldwide, prospective longitudinal study focused squarely on BD and its heterogeneous presentations will serve as a platform for discovery and promote major advances toward optimizing outcomes for every individual with this illness.Reprinted from Bipolar Disord 2022; 24:709-719, with permission from John Wiley and Sons. Copyright © 2022.

Real-World Experiences with Taliglucerase Alfa Home Infusions for Patients with Gaucher Disease: A Global Cohort Study.

Taliglucerase alfa is an enzyme replacement therapy approved for Gaucher disease. We assessed the duration/compliance/safety of such home infusions in commercial use in four countries where home infusion programs are available. The treatment duration/compliance study included 173 patients (Israel, 58; US, 61; Brazil, 48; Australia, 6) who received ≥1 taliglucerase alfa home infusion through 6/2021. The median age at home therapy initiation was 38 (range, 2-87) years; 58% were females. The median treatment duration (at home) was 2.7 (range, 0.04-9.0) years. The annual compliance rate was stable (≥95%) throughout the study period. A search of the Pfizer global safety database (through 6/2021), identified 19 adverse events (AEs) as related to "definite home use" and 14 to "possible home use" of taliglucerase alfa; 42.4% of these AEs were serious; none were fatal. Twelve serious AEs in five separate case reports were considered treatment related: one case of chest discomfort/pain and hypertension and one case of erythema associated with a toe blister, for which causality could not be excluded; pain in extremity; projectile vomiting and chills, alongside excessive eye blinking; and an infusion-related AE (pruritus). In conclusion, this real-life global study demonstrated that taliglucerase alfa home infusions are safe with high compliance rates.

Disease burden of chronic kidney disease attributable to lead exposure: A global analysis of 30 years since 1990

BackgroundExposure to lead (Pb) is associated with an increased risk of chronic kidney disease (CKD). However, limited studies explored the global burden of CKD attributable to Pb exposure, especially in countries with different development levels. This study aimed to comprehensively evaluate the temporal and spatial trend in the disease burden of CKD attributable to Pb exposure in 204 countries and territories from 1990 to 2019. MethodsWe used the data from Global Burden of Disease Study (GBD) 2019 to estimate annual deaths, disability-adjusted life years (DALYs), age-standardized mortality rates (ASMR), and age-standardized DALYs rate (ASDR) of CKD attributable to Pb exposure. The annual average percentage change (AAPCs) was calculated using the Joinpoint model to evaluate the changing trend of CKD ASMR and ASDR attributable to Pb exposure from 1990 to 2019. Meanwhile, age-period-cohort (APC) model was used to assess changes in the mortality of CKD attributable to Pb exposure from 1990 to 2019. ResultsGlobal ASMR for CKD attributable to Pb exposure trended upward from 1990 to 2019. ASMR and ASDR were the highest in low and low-middle SDI regions. With the APC model, we found that global mortality rates for CKD attributable to Pb exposure increased with age. The global period rate ratio showed the highest value in 2000–2004 and the lowest in 2015–2019, while the global cohort rate ratio showed the highest value in 1941–1949 and the lowest during 1986–1994. ConclusionsFrom 1990 to 2019, the global burden of CKD attributable to Pb exposure increased globally, especially in low and low-middle SDI regions, as well as the elderly. Pb exposure is still a great threat to the global burden of CKD, and the implementation of effective prevention measures to reduce Pb exposure in the environment should be continually strengthened.

Clinical Outcomes of Patients with Multiple Myeloma after Daratumumab Failure.

Anti-CD38 monoclonal antibody (MoAB) therapy has significantly improved the prognosis of patients with multiple myeloma. However, not all patients sustain durable responses. We aimed to describe the natural history of patients relapsed or refractory (R/R) to CD38 MoAB therapy. We performed a single-center, retrospective analysis of the clinical characteristics and outcomes of 81 patients with multiple myeloma who progressed after treatment with daratumumab. Our cohort was heavily pretreated, with a median of two lines prior to daratumumab and only 17 patients received daratumumab as a first line. A total of 38.2% had received a previous autologous stem cell transplantation (ASCT), and 61.7% had received both an immunomodulatory drug (IMID) and a proteasome inhibitor (PI). The median overall survival (OS) was 21 months for the global cohort but it decreased to 14 months for triple-class refractory patients and 5 months for penta-refractory patients. Most of the patients (83.9%) received treatment after daratumumab progression, in many cases with second generation IMID or PI, but seven patients were treated with anti-BCMA therapy and three patients received CART therapy within a clinical trial. In conclusion, patients R/R to daratumumab represent an unmet clinical need with poor prognosis and in need of incorporation of new treatments.

Global Effect of Modifiable Risk Factors on Cardiovascular Disease and Mortality

BackgroundFive modifiable risk factors are associated with cardiovascular disease and death from any cause. Studies using individual-level data to evaluate the regional and sex-specific prevalence of the risk factors and their effect on these outcomes are lacking.MethodsWe pooled and harmonized individual-level data from 112 cohort studies conducted in 34 countries and 8 geographic regions participating in the Global Cardiovascular Risk Consortium. We examined associations between the risk factors (body-mass index, systolic blood pressure, non–high-density lipoprotein cholesterol, current smoking, and diabetes) and incident cardiovascular disease and death from any cause using Cox regression analyses, stratified according to geographic region, age, and sex. Population-attributable fractions were estimated for the 10-year incidence of cardiovascular disease and 10-year all-cause mortality.ResultsAmong 1,518,028 participants (54.1% of whom were women) with a median age of 54.4 years, regional variations in the prevalence of the five modifiable risk factors were noted. Incident cardiovascular disease occurred in 80,596 participants during a median follow-up of 7.3 years (maximum, 47.3), and 177,369 participants died during a median follow-up of 8.7 years (maximum, 47.6). For all five risk factors combined, the aggregate global population-attributable fraction of the 10-year incidence of cardiovascular disease was 57.2% (95% confidence interval [CI], 52.4 to 62.1) among women and 52.6% (95% CI, 49.0 to 56.1) among men, and the corresponding values for 10-year all-cause mortality were 22.2% (95% CI, 16.8 to 27.5) and 19.1% (95% CI, 14.6 to 23.6).ConclusionsHarmonized individual-level data from a global cohort showed that 57.2% and 52.6% of cases of incident cardiovascular disease among women and men, respectively, and 22.2% and 19.1% of deaths from any cause among women and men, respectively, may be attributable to five modifiable risk factors. (Funded by the German Center for Cardiovascular Research (DZHK); ClinicalTrials.gov number, NCT05466825.)

Patterns of oral anticoagulant use and outcomes in Asian patients with atrial fibrillation: a post-hoc analysis from the GLORIA-AF Registry

Previous studies suggested potential ethnic differences in the management and outcomes of atrial fibrillation (AF). We aim to analyse oral anticoagulant (OAC) prescription, discontinuation, and risk of adverse outcomes in Asian patients with AF, using data from a global prospective cohort study. From the GLORIA-AF Registry Phase II-III (November 2011-December 2014 for Phase II, and January 2014-December 2016 for Phase III), we analysed patients according to their self-reported ethnicity (Asian vs. non-Asian), as well as according to Asian subgroups (Chinese, Japanese, Korean and other Asian). Logistic regression was used to analyse OAC prescription, while the risk of OAC discontinuation and adverse outcomes were analysed through Cox-regression model. Our primary outcome was the composite of all-cause death and major adverse cardiovascular events (MACE). The original studies were registered with ClinicalTrials.gov, NCT01468701, NCT01671007, and NCT01937377. 34,421 patients were included (70.0±10.5 years, 45.1% females, 6900 (20.0%) Asian: 3829 (55.5%) Chinese, 814 (11.8%) Japanese, 1964 (28.5%) Korean and 293 (4.2%) other Asian). Most of the Asian patients were recruited in Asia (n=6701, 97.1%), while non-Asian patients were mainly recruited in Europe (n=15,449, 56.1%) and North America (n=8378, 30.4%). Compared to non-Asian individuals, prescription of OAC and non-vitamin K antagonist oral anticoagulant (NOAC) was lower in Asian patients (Odds Ratio [OR] and 95% Confidence Intervals (CI): 0.23 [0.22-0.25] and 0.66 [0.61-0.71], respectively), but higher in the Japanese subgroup. Asian ethnicity was also associated with higher risk of OAC discontinuation (Hazard Ratio [HR] and [95% CI]: 1.79 [1.67-1.92]), and lower risk of the primary composite outcome (HR [95% CI]: 0.86 [0.76-0.96]). Among the exploratory secondary outcomes, Asian ethnicity was associated with higher risks of thromboembolism and intracranial haemorrhage, and lower risk of major bleeding. Our results showed that Asian patients with AF showed suboptimal thromboembolic risk management and a specific risk profile of adverse outcomes; these differences may also reflect differences in country-specific factors. Ensuring integrated and appropriate treatment of these patients is crucial to improve their prognosis. The GLORIA-AF Registry was funded by Boehringer Ingelheim GmbH.

Risk of comorbid autoimmune diseases in patients with immunobullous disorders: A global large-scale cohort study

Risk of comorbid autoimmune diseases in patients with immunobullous disorders: A global large-scale cohort study

Autonomous cortisol secretion in patients with primary aldosteronism: prevalence and implications on cardiometabolic profile and on surgical outcomes.

The aim of this study was to evaluate the prevalence of autonomous cortisol secretion (ACS) in patients with primary aldosteronism (PA) and its implications on cardiometabolic and surgical outcomes. This is a retrospective multicenter study of PA patients who underwent 1 mg dexamethasone-suppression test (DST) during diagnostic workup in 21 Spanish tertiary hospitals. ACS was defined as a cortisol post-DST >1.8 µg/dL (confirmed ACS if >5 µg/dL and possible ACS if 1.8-5 µg/dL) in the absence of specific clinical features of hypercortisolism. The cardiometabolic profile was compared with a control group with ACS without PA (ACS group) matched for age and DST levels. The prevalence of ACS in the global cohort of patients with PA (n = 176) was 29% (ACS-PA; n = 51). Ten patients had confirmed ACS and 41 possible ACS. The cardiometabolic profile of ACS-PA and PA-only patients was similar, except for older age and larger tumor size of the adrenal lesion in the ACS-PA group. When comparing the ACS-PA group (n = 51) and the ACS group (n = 78), the prevalence of hypertension (OR 7.7 (2.64-22.32)) and cardiovascular events (OR 5.0 (2.29-11.07)) was higher in ACS-PA patients than in ACS patients. The coexistence of ACS in patients with PA did not affect the surgical outcomes, the proportion of biochemical cure and clinical cure being similar between ACS-PA and PA-only groups. Co-secretion of cortisol and aldosterone affects almost one-third of patients with PA. Its occurrence is more frequent in patients with larger tumors and advanced age. However, the cardiometabolic and surgical outcomes of patients with ACS-PA and PA-only are similar.

Factores asociados a ventilación mecánica prolongada en niños con fallo respiratorio de causa pulmonar: Estudio de cohortes del registro de LARed Network

ObjectivesTo identify factors associated with prolonged mechanical ventilation (pMV) in pediatric patients in pediatric intensive care units (PICUs). DesignSecondary analysis of a prospective cohort. SettingPICUs in centers that are part of the LARed Network between April 2017 and January 2022. ParticipantsPediatric patients on mechanical ventilation (IMV) due to respiratory causes. We defined IMV time greater than the 75th percentile of the global cohort. InterventionsNone. Main variables of interestDemographic data, diagnoses, severity scores, therapies, complications, length of stay, morbidity, and mortality. ResultsOne thousand 6hundred and ninety 8children with MV of 8±7 days were included, and pIMV was defined as 9 days. Factors related to admission were age under 6 months (OR 1.61, 95% CI 1.17–2.22), bronchopulmonary dysplasia (OR 3.71, 95% CI 1.87–7.36), and fungal infections (OR 6.66, 95% CI 1.87–23.74), while patients with asthma had a lower risk of pIMV (OR 0.30, 95% CI 0.12–0.78). Regarding evolution and length of stay in the PICU, it was related to ventilation-associated pneumonia (OR 4.27, 95% CI 1.79–10.20), need for tracheostomy (OR 2.91, 95% CI 1.89–4.48), transfusions (OR 2.94, 95% CI 2.18–3.96), neuromuscular blockade (OR 2.08, 95% CI 1.48–2.93), high-frequency ventilation (OR 2.91, 95% CI 1.89–4.48), and longer PICU stay (OR 1.13, 95% CI 1.10–1.16). In addition, mean airway pressure greater than 13cmH2O was associated with pIMV (OR 1.57, 95% CI 1.12–2.21). ConclusionsFactors related to IMV duration greater than 9 days in pediatric patients in PICUs were identified in terms of admission, evolution, and length of stay.