Abstract
Background
Pulmonary arterial hypertension (PAH) is a syndrome characterized by marked remodeling of the pulmonary vasculature and leading to right heart failure and death. Selexipag, an ...oral prostacyclin IP receptor agonist, has been shown to decrease morbidity and mortality compared to patients treated with placebo.
Purpose
Our aim was to evaluate the efficacy and safety of Selexipag in patients with PAH in real-life.
Methods
The RAMPHA study was a multicenter, observational and retrospective trial of patients who had PAH and began taking Selexipag between 2017–2021. We analyzed baseline characteristics, risk profiles, clinical assessments that were used for risk stratification and events in follow-up time.
Results
29 patients aged 48±14 were initially studied. 23 (79%) were women. Within the pulmonary hypertension-classification, 10 (34,5%) had PAH associated-congenital heart disease, 9 (31%) had idiopathic HAP, 7 (24,1%) had PAH associated with connective tissue disease, 1 had PAH associated to HIV and 2 heritable PAH. The time from PAH diagnoses to the beginning of Selexipag treatment was 54 months (IQR 89).
89,7% (26) were in treatment with doubled combination therapy with PDE5i+ARE; Sildenafil was the most widely used PDE5i and bosentan (37,9%) the most used ARE. No patients were under treatment with intravenous prostacyclin analogue, but 3 were with Treprostinil (1 of them subcutaneous and 2 inhaled) and 2 patients with iloprost.
Most patients were categorized in intermediate risk profile (figure 1), using the risk stratification strategy of ESC/ERS PH guidelines. In the approach of risk assessment before start with Selexipag, clinical, functional, exercise (with 6MWT) and echocardiographic variables were used in all the patients. Biochemical variables with NT-proBNP were used in 93% of the patients. Only 15 patients had a right catheterization to get haemodynamic parameters before the treatment.
At follow up, 11 patients (38%) improved functional class, only 1 patient got worst (p=0,001). 3 patients improved risk-profile in the exercise test and, in the others, a quantitative improvement was found. NT-proBNP levels were not significant better (924ng/l IQR 1209 vs 760ng/l IQR 1397). There were not changes in RV function in the echocardiographic parameters.
Selexipag was well-tolerated, 86% of the patients experienced side effects, but none had to discountinue the treatment. The most common side effect was headache. The titration lasted 68 days (IQR 72) and 38% of the patients got maximum doses.
At the medium-term follow-up of 52 months, the free-event survival (worsening of PAH that resulted in hospitalization; initiation of parenteral prostanoid therapy or death to PAH; or any cause) was 80% (Figure 2).
Conclusion
Selexipag, added as triple combination therapy in patients with PAH intermediate risk, improved risk variables, was well tolerated and achieved a medium-long-term free-event survival greater than 80%.
Funding Acknowledgement
Type of funding sources: None.
To identify patterns (clusters) of damage manifestation within a large cohort of juvenile SLE (jSLE) patients and evaluate their possible association with mortality.
This is a multicentre, ...descriptive, cross-sectional study of a cohort of 345 jSLE patients from the Spanish Society of Rheumatology Lupus Registry. Organ damage was ascertained using the Systemic Lupus International Collaborating Clinics Damage Index. Using cluster analysis, groups of patients with similar patterns of damage manifestation were identified and compared.
Mean age (years) ± S.D. at diagnosis was 14.2 ± 2.89; 88.7% were female and 93.4% were Caucasian. Mean SLICC/ACR DI ± S.D. was 1.27 ± 1.63. A total of 12 (3.5%) patients died. Three damage clusters were identified: Cluster 1 (72.7% of patients) presented a lower number of individuals with damage (22.3% vs. 100% in Clusters 2 and 3, P < 0.001); Cluster 2 (14.5% of patients) was characterized by renal damage in 60% of patients, significantly more than Clusters 1 and 3 (P < 0.001), in addition to increased more ocular, cardiovascular and gonadal damage; Cluster 3 (12.7%) was the only group with musculoskeletal damage (100%), significantly higher than in Clusters 1 and 2 (P < 0.001). The overall mortality rate in Cluster 2 was 2.2 times higher than that in Cluster 3 and 5 times higher than that in Cluster 1 (P < 0.017 for both comparisons).
In a large cohort of jSLE patients, renal and musculoskeletal damage manifestations were the two dominant forms of damage by which patients were sorted into clinically meaningful clusters. We found two clusters of jSLE with important clinical damage that were associated with higher rates of mortality, especially for the cluster of patients with predominant renal damage. Physicians should be particularly vigilant to the early prevention of damage in this subset of jSLE patients with kidney involvement.
Abstract
Background
Sex differences are known to exist in the management of women presenting with ST elevation myocardial infarction (STEMI).Few studies have examined whether the clinical management ...and prognosis differs by sex when the STEMI network system is applied.
Purpose
To assess whether the STEMI network system improves management and prognosis both in men and women in Spain and to analyze possible differences according to sex.
Methods
We conducted a retrospective longitudinal study using information provided by the minimal database system (MDBS) of the Spanish National Health System (SNHS) to identify all hospitalizations in patients aged 35–94 years with the principal diagnosis of STEMI from 2005–2015. The risk-standardized in-hospital mortality ratio (RSMR) was defined as the ratio between predicted mortality and expected mortality, multiplied by the crude rate of mortality. The RSMR was calculated using multilevel risk adjustment models developed by the Medicare and Medicaid Services. The year of the development of organized systems of care for STEMI patients in the different Autonomous Communities was double-checked using data from the National Cardiac Catheterization and Interventional Cardiology Annual Registry. RSMR was used to compare outcomes related with gender and with the presence of regional AMI networks and the performance of PCI. Temporal trends for in-hospital mortality during the observed period were modeled using Poisson regression analysis with year as the only independent variable. In all models, incidence rate ratios (IRR) and their 95% confidence intervals (95% CI) were calculated.
Results
A total of 325,017 STEMI were identified among patients aged 35–94 years old. Of them 273,182 were selected after exclusions, and 106,277 (38.8%) were women. Women were on average 10 years older than men and had more comorbidities burden. The overall proportion of STEMI patients underwent to PCI increased, when a regional STEMI network was present from 2005–2015: (63.7% vs 48.2% in men; and 47.4% vs 32.9% in women; p<0.001). Differences in crude mortality between sexes was 15%, maintaining through 10 years, despite a higher increased of PCI (figure 1).However, women were less likely to be treated with PCI even though when STEMI network was stablished (63.7% vs 48.2% in men, 47.4% vs 32.9% in women, p<0.001) (figure 1).The mean crude in-hospital mortality rate for the whole study period was higher in women (9.3% vs 18.3%; unadjusted OR: 2.18, 95% CI: 2.12.-2.23, p<0.0001). RSMR was lower for women when STEMI network were working (17.7% vs. 19.7%; p<0.001).PCI and the presence of STEMI network were associated with a lower in-hospital mortality in STEMI women (adjusted OR, 0.48; 95% CI 0.41–0.52 and OR, 0.84; 95% CI 0.79–0.89, p<0.001, respectively).
Conclusions
Women were less likely to be treated with PCI and had higher in-hospital risk-adjusted mortality than men, despite the existence of STEMI network system.
Abstract
Background
Recent studies reported a decrease in the mortality of ST-elevation myocardial infarction (STEMI) patients. This favorable evolution could not extend to women. The interaction ...between gender and mortality in STEMI remains controversial.
Purpose
To assess the impact of female sex on mortality of patients with STEMI through of period of 11 years.
Methods
We conducted a retrospective longitudinal study using information provided by the minimal database system of the Spanish National Health System to identify all hospitalizations in patients aged 35–94 years with the principal diagnosis of STEMI from 2005–2015.
Results
A total of 325,017 STEMI were identified. Of them, 273,182 were included, and 106,277 (38.8%) were women. Women were older than men and had more comorbidities. Through the study period 53% men vs 37.2% underwent PTCA; women presented more frequently heart failure, shock and stroke than men (p<0.001, respectively). The mean crude in-hospital mortality rate for the whole study period was higher in women (OR: 2.18; 95% CI: 2.12.-2.23, p<0.0001). Female sex was independently associated with higher in-hospital mortality (adjusted OR: 1.18; 95% CI: 1.14–1.22, p<0.001) (Table 1). The risk was maintained through the whole study period (lower OR: 1.14 in 2014; higher OR: 1.28 in 2006).
Table 1. Variables independently associated with in-hospital mortality adjusted by risk in a multilevel logistic regression model, 2005–2015
STEMI In-hospital mortality
Odds Ratio
P
95% CI
Woman
1.18
<0.001
1.14
1.22
Age
1.06
<0.001
1.06
1.06
History of PTCA
1.58
<0.001
1.40
1.77
Congestive heart failure
1.26
<0.001
1.22
1.30
Acute Myocardial Infarction
1.84
<0.001
1.54
2.20
Anterior myocardial infarction
1.47
<0.001
1.23
1.76
Cardio-respiratory failure or shock
15.25
<0.001
14.78
15.75
Hypertension
0.81
<0.001
0.79
0.84
Stroke
5.76
<0.001
5.18
6.42
Cerebrovascular disease
0.86
<0.001
0.79
0.93
Renal failure
1.95
<0.001
1.88
2.02
Vascular disease and complications
7.03
<0.001
5.72
8.63
CI, Confidence Interval.
Conclusions
Female sex is an independent predictor of mortality in patients with STEMI in Spain, maintaining through a period of the 11 years.
The burden of tuberculosis (TB) disease among household contacts of multidrug-resistant TB (MDR-TB) patients is poorly understood and might represent a target for transmission-interrupting ...interventions.
This retrospective cohort study, conducted in Lima, Peru, from June to September 2008, estimated the incidence of TB disease among household contacts of MDR-TB patients in 358 households.
Of 2112 household contacts in 80 households (22% of households), 108 (5%) developed TB disease during the study, giving an incidence rate of 2360 per 100 000 contact follow-up years for each of the first 3 years after exposure. Drug susceptibility tests (DST) were available for 50 diseased contacts, of whom 36 (80%) had MDR-TB. Forty-two pairs of index-contact DSTs were available, among which the contact had an identical or less resistant phenotype than the index case in 27 pairs. Multivariate Cox regression demonstrated that male contacts (hazard ratio HR 2.8, P < 0.05), with previous TB disease (HR 20.7, P < 0.001) and with associated (non-human immunodeficiency virus) comorbidities (HR 11.2, P < 0.001) were more likely to develop TB.
The high percentage of diseased household contacts highlights an opportunity for household-level interventions to prevent transmission, whether or not these cases were all attributable to the index case.
Circulating insulin‐like growth factors (IGFs) and their binding proteins (IGFBPs) are associated with prostate cancer. Using genetic variants as instruments for IGF peptides, we investigated whether ...these associations are likely to be causal. We identified from the literature 56 single nucleotide polymorphisms (SNPs) in the IGF axis previously associated with biomarker levels (8 from a genome‐wide association study GWAS and 48 in reported candidate genes). In ∼700 men without prostate cancer and two replication cohorts (N ∼ 900 and ∼9,000), we examined the properties of these SNPS as instrumental variables (IVs) for IGF‐I, IGF‐II, IGFBP‐2 and IGFBP‐3. Those confirmed as strong IVs were tested for association with prostate cancer risk, low (< 7) vs. high (≥ 7) Gleason grade, localised vs. advanced stage, and mortality, in 22,936 controls and 22,992 cases. IV analysis was used in an attempt to estimate the causal effect of circulating IGF peptides on prostate cancer. Published SNPs in the IGFBP1/IGFBP3 gene region, particularly rs11977526, were strong instruments for IGF‐II and IGFBP‐3, less so for IGF‐I. Rs11977526 was associated with high (vs. low) Gleason grade (OR per IGF‐II/IGFBP‐3 level‐raising allele 1.05; 95% CI: 1.00, 1.10). Using rs11977526 as an IV we estimated the causal effect of a one SD increase in IGF‐II (∼265 ng/mL) on risk of high vs. low grade disease as 1.14 (95% CI: 1.00, 1.31). Because of the potential for pleiotropy of the genetic instruments, these findings can only causally implicate the IGF pathway in general, not any one specific biomarker.
What's New?
Circulating insulin‐like growth factors (IGF) and their binding proteins have been associated with prostate cancer risk in observational epidemiological studies but it is not clear whether there is a causal relationship with disease. To address this question, the authors used Mendelian randomization, a method that uses genetic variants as proxies for measured exposures. Their results implicate the IGF pathway in general in prostate cancer development but specific biomarkers remain to be determined.
This study reports length‐weight relationships and growth parameters for Floridichthys polyommus Hubbs, 1936 and Fundulus persimilis Miller, 1955 from La Carbonera, a karstic tropical coastal lagoon ...on the northwestern coast of the Yucatan Peninsula, Mexico. Specimens were collected between April 2009 and March 2010. The resulting length‐weight relationship for F. polyommus was: W = 0.0180 Lt³.³⁷ and W = 0.0142 Lt³.³⁵ for F. persimilis. This study presents the first estimation for both species of the von Bertalanffy growth model parameters, the growth performance index, the L₅₀, and is the first report of the length‐weight relationship for F. persimilis.
The antineutrino scattering channel v¯μCH→μ+π−X (nucleon(s)) is analyzed in the incident energy range 1.5 to 10 GeV using the MINERvA detector at Fermilab. Differential cross sections are reported as ...functions of μ+ momentum and production angle, π− kinetic energy and production angle, and antineutrino energy and squared four-momentum transfer. Distribution shapes are generally reproduced by simulations based on the GENIE, NuWro, and GiBUU event generators, however GENIE (GiBUU) overestimates (underestimates) the cross section normalizations by 8% (10%). Comparisons of data with the GENIE-based reference simulation probe conventional treatments of cross sections and pion intranuclear rescattering. The distribution of nontrack vertex energy is used to decompose the signal sample into reaction categories, and cross sections are determined for the exclusive reactions μ+π−n and μ+π−p. A similar treatment applied to the published MINERvA sample v¯μCH→μ+π0Xnucleon(s) has determined the μ+π0n cross section, and the latter is used with σ(π−n) and σ(π−p) to carry out an isospin decomposition of v¯μ-induced CC(π). The ratio of magnitudes and relative phase for isospin amplitudes A3 and A1 thereby obtained are: Rv¯=0.99±0.19 and ϕv¯=93°±7°. Our results are in agreement with bubble chamber measurements made four decades ago.
Transmission of Zika virus (ZIKV) in the Americas was first confirmed in May 2015 in northeast Brazil. Brazil has had the highest number of reported ZIKV cases worldwide (more than 200,000 by 24 ...December 2016) and the most cases associated with microcephaly and other birth defects (2,366 confirmed by 31 December 2016). Since the initial detection of ZIKV in Brazil, more than 45 countries in the Americas have reported local ZIKV transmission, with 24 of these reporting severe ZIKV-associated disease. However, the origin and epidemic history of ZIKV in Brazil and the Americas remain poorly understood, despite the value of this information for interpreting observed trends in reported microcephaly. Here we address this issue by generating 54 complete or partial ZIKV genomes, mostly from Brazil, and reporting data generated by a mobile genomics laboratory that travelled across northeast Brazil in 2016. One sequence represents the earliest confirmed ZIKV infection in Brazil. Analyses of viral genomes with ecological and epidemiological data yield an estimate that ZIKV was present in northeast Brazil by February 2014 and is likely to have disseminated from there, nationally and internationally, before the first detection of ZIKV in the Americas. Estimated dates for the international spread of ZIKV from Brazil indicate the duration of pre-detection cryptic transmission in recipient regions. The role of northeast Brazil in the establishment of ZIKV in the Americas is further supported by geographic analysis of ZIKV transmission potential and by estimates of the basic reproduction number of the virus.
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