Antiretroviral therapy has led to a decrease in HIV-related mortality and to the emergence of non-AIDS defining diseases as competing causes of death. This study estimates the HIV mortality rate and ...their risk factors with regard to different causes in a large city from January 2001 to June 2013.
We followed-up 3137 newly diagnosed HIV non-AIDS cases. Causes of death were classified as HIV-related, non-HIV-related and external. We examined the effect of risk factors on survival using mortality rates, Kaplan-Meier plots and Cox models. Finally, we estimated survival for each main cause of death groups through Fine and Gray models.
182 deaths were found 14.0/1000 person-years of follow-up (py); 95% confidence interval (CI):12.0-16.1/1000 py, 81.3% of them had a known cause of death. Mortality rate by HIV-related causes and non-HIV-related causes was the same (4.9/1000 py; CI:3.7-6.1/1000 py), external was lower 1.7/1000 py; (1.0-2.4/1000 py).
Kaplan-Meier estimate showed worse survival in intravenous drug user (IDU) and heterosexuals than in men having sex with men (MSM). Factors associated with HIV-related causes of death include: IDU male (subHazard Ratio (sHR):3.2; CI:1.5-7.0) and <200 CD4 at diagnosis (sHR:2.7; CI:1.3-5.7) versus ≥500 CD4. Factors associated with non-HIV-related causes of death include: ageing (sHR:1.5; CI:1.4-1.7) and heterosexual female (sHR:2.8; CI:1.1-7.3) versus MSM. Factors associated with external causes of death were IDU male (sHR:28.7; CI:6.7-123.2) and heterosexual male (sHR:11.8; CI:2.5-56.4) versus MSM.
There are important differences in survival among transmission groups. Improved treatment is especially necessary in IDUs and heterosexual males.
A 51-year-old woman was given a diagnosis of primary retroperitoneal synovial sarcoma, which was surgically removed, and she was subsequently treated with chemotherapy and radiotherapy. Five years ...later, the patient was readmitted with a 1-month history of progressive dyspnea and was initially given a diagnosis of bilateral pulmonary embolism. Angiography performed some time later revealed progression of the previous filling defects and the appearance of two new nodular endovascular images. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) was performed, and the cytologic analysis of the cell aspirate was compatible with endovascular metastatic sarcoma. In conclusion, EBUS-TBNA in the appropriate setting is an effective method for sampling endovascular lesions, adding pathologic information and allowing for early and accurate diagnosis.
Under-diagnosis of COPD is an important unmet medical need. We investigated the characteristics and prognosis of hospitalised patients with undiagnosed COPD.
The PAC-COPD cohort included 342 COPD ...patients hospitalised for the first time for an exacerbation of COPD (2004-2006). Patients were extensively characterised using sociodemographic, clinical and functional variables, and the cohort was followed-up through 2008. We defined "undiagnosed COPD" by the absence of any self-reported respiratory disease and regular use of any pharmacological respiratory treatment.
Undiagnosed COPD was present in 34% of patients. They were younger (mean age 66 vs. 68 years, p = 0.03), reported fewer symptoms (mMRC dyspnoea score, 2.1 vs. 2.6, p < 0.01), and had a better health status (SGRQ total score, 29 vs. 40, p < 0.01), milder airflow limitation (FEV1% ref., 59% vs. 49%, p < 0.01), and fewer comorbidities (two or more, 40% vs. 56%, p < 0.01) when compared with patients with an established COPD diagnosis. Three months after hospital discharge, 16% of the undiagnosed COPD patients had stopped smoking (vs. 5%, p = 0.019). During follow-up, annual hospitalisation rates were lower in undiagnosed COPD patients (0.14 vs. 0.25, p < 0.01); however, this difference disappeared after adjustment for severity. Mortality was similar in both groups.
Undiagnosed COPD patients have less severe disease and lower risk of re-hospitalisation when compared with hospitalised patients with known COPD.
Beta-3 adrenergic receptor (β3AR) agonists have been shown to produce vasodilation and prevention of ventricular remodeling in different conditions. Given that these biological functions are critical ...in pulmonary hypertension (PH), we aimed to demonstrate a beneficial effect of β3AR agonists in PH. An experimental study in pigs (
n
= 34) with chronic PH created by pulmonary vein banding was designed to evaluate the acute hemodynamic effect and the long-term effect of β3AR agonists on hemodynamics, vascular remodeling and RV performance in chronic PH. Ex vivo human experiments were performed to explore the expression of β3AR mRNA and the vasodilator response of β3AR agonists in pulmonary arteries. Single intravenous administration of the β3AR agonist BRL37344 produced a significant acute reduction in PVR, and two-weeks treatment with two different β3AR selective agonists, intravenous BRL37344 or oral mirabegron, resulted in a significant reduction in PVR (median of −2.0 Wood units/m
2
for BRL37344 vs. +1.5 for vehicle,
p
= 0.04; and −1.8 Wood units/m
2
for mirabegron vs. +1.6 for vehicle,
p
= 0.002) associated with a significant improvement in magnetic resonance-measured RV performance. Histological markers of pulmonary vascular proliferation (p27 and Ki67) were significantly attenuated in β3AR agonists-treated pigs. β3AR was expressed in human pulmonary arteries and β3AR agonists produced vasodilatation. β3AR agonists produced a significant reduction in PVR and improved RV performance in experimental PH, emerging as a potential novel approach for treating patients with chronic PH.
The aim of this study was to determine the evolution of HIV infection, gonorrhea, syphilis and lymphogranuloma venereum (LGV), and their epidemiological characteristics in Barcelona city.
...Population-based incidence study of all newly occurring diagnoses of HIV infection, syphilis, gonorrhea and LGV detected in Barcelona between January 2007 and December 2011. A descriptive analysis was performed. The annual incidence rates per 100,000 inhabitants were calculated by sex, sexual conduct and educational level. To estimate global sex-specific rates we used the Barcelona city census; for the calculation of rates by sexual conduct and educational level we used estimates of the Barcelona Health Interview Survey. Trends were analysed using the chi-squared test for linear trend.
HIV. 66.8 % of the HIV cases were men who had sex with men (MSM). The incidence rates in MSM over the study period were from 692.67/100,000 to 909.88/100,000 inh. Syphilis. 74.2 % of the syphilis cases were MSM. The incidence rates in MSM were from 224.9/100,000 to 891.97/100,000 inh. and the MSM with a university education ranged from 196.3/100,000 to 1020.8/100,000. Gonorrhea. 45.5 % of the gonorrhea cases were MSM. The incidence rates in MSM were from 164.24/100,000 to 404.79/100,000 inh. and the MSM with university education ranged from 176.7/100,000 to 530.1/100,000 inh.. Lymphogranuloma venereum (LGV). 95.3 % of the LGV cases are MSM. The incidence rates in MSM were from 24.99/100,000 to 282.99/100,000 inh. and the MSM with university education ranged from 9.3/100,000 to 265/100,000 inh.
An increase in cases of STI was observed. These STI mainly affected MSM with a university education. Continuing to monitor changes in the epidemiology of STI, and identifying the most affected groups should permit redesigning preventive programs, with the goal of finding the most efficient way to reach these population groups.
The European Respiratory Society (ERS) Research Seminar entitled "Pulmonary vascular endothelium: orchestra conductor in respiratory diseases - highlights from basic research to therapy" brought ...together international experts in dysfunctional pulmonary endothelium, from basic science to translational medicine, to discuss several important aspects in acute and chronic lung diseases. This review will briefly sum up the different topics of discussion from this meeting which was held in Paris, France on October 27-28, 2016. It is important to consider that this paper does not address all aspects of endothelial dysfunction but focuses on specific themes such as: 1) the complex role of the pulmonary endothelium in orchestrating the host response in both health and disease (acute lung injury, chronic obstructive pulmonary disease, high-altitude pulmonary oedema and pulmonary hypertension); and 2) the potential value of dysfunctional pulmonary endothelium as a target for innovative therapies.
Aims
Pulmonary hypertension (PH) associated with left heart disease is an increasingly prevalent problem, orphan of targeted therapies, and related to a poor prognosis, particularly when pre‐ and ...post‐capillary PH combine. The current study aimed to determine whether treatment with the selective β3 adrenoreceptor agonist mirabegron improves outcomes in patients with combined pre‐ and post‐capillary PH (CpcPH).
Methods and results
The β3 Adrenergic Agonist Treatment in Chronic Pulmonary Hypertension Secondary to Heart Failure (SPHERE‐HF) trial is a multicentre, randomized, parallel, placebo‐controlled clinical trial that enrolled stable patients with CpcPH associated with symptomatic heart failure. A total of 80 patients were assigned to receive mirabegron (50 mg daily, titrated till 200 mg daily, n = 39) or placebo (n = 41) for 16 weeks. Of them, 66 patients successfully completed the study protocol and were valid for the main analysis. The primary endpoint was the change in pulmonary vascular resistance (PVR) on right heart catheterization. Secondary outcomes included the change in right ventricular (RV) ejection fraction by cardiac magnetic resonance or computed tomography, other haemodynamic variables, functional class, and quality of life. The trial was negative for the primary outcome (placebo‐corrected mean difference of 0.62 Wood units, 95% confidence interval CI −0.38, 1.61, p = 0.218). Patients receiving mirabegron presented a significant improvement in RV ejection fraction as compared to placebo (placebo‐corrected mean difference of 3.0%, 95% CI 0.4, 5.7%, p = 0.026), without significant differences in other pre‐specified secondary outcomes.
Conclusions
SPHERE‐HF is the first clinical trial to assess the potential benefit of β3 adrenergic agonists in PH. The trial was negative since mirabegron did not reduce PVR, the primary endpoint, in patients with CpcPH. On pre‐specified secondary outcomes, a significant improvement in RV ejection fraction assessed by advanced cardiac imaging was found, without differences in functional class or quality of life.
Summary of the study outline, flowchart, and results of the primary and secondary outcomes. The β3 selective agonist mirabegron did not improve pulmonary haemodynamics in adult patients with combined pre‐ and post‐capillary pulmonary hypertension associated with symptomatic heart failure. On secondary outcomes, a significant improvement in right ventricular ejection fraction assessed by advanced cardiac imaging was found, without differences in functional class or quality of life. PP, per protocol population.
Data on the effect of initial combination therapy with ambrisentan and tadalafil on long-term outcomes in patients with pulmonary arterial hypertension are scarce.
In this event-driven, double-blind ...study, we randomly assigned, in a 2:1:1 ratio, participants with World Health Organization functional class II or III symptoms of pulmonary arterial hypertension who had not previously received treatment to receive initial combination therapy with 10 mg of ambrisentan plus 40 mg of tadalafil (combination-therapy group), 10 mg of ambrisentan plus placebo (ambrisentan-monotherapy group), or 40 mg of tadalafil plus placebo (tadalafil-monotherapy group), all administered once daily. The primary end point in a time-to-event analysis was the first event of clinical failure, which was defined as the first occurrence of a composite of death, hospitalization for worsening pulmonary arterial hypertension, disease progression, or unsatisfactory long-term clinical response.
The primary analysis included 500 participants; 253 were assigned to the combination-therapy group, 126 to the ambrisentan-monotherapy group, and 121 to the tadalafil-monotherapy group. A primary end-point event occurred in 18%, 34%, and 28% of the participants in these groups, respectively, and in 31% of the pooled-monotherapy group (the two monotherapy groups combined). The hazard ratio for the primary end point in the combination-therapy group versus the pooled-monotherapy group was 0.50 (95% confidence interval CI, 0.35 to 0.72; P<0.001). At week 24, the combination-therapy group had greater reductions from baseline in N-terminal pro-brain natriuretic peptide levels than did the pooled-monotherapy group (mean change, -67.2% vs. -50.4%; P<0.001), as well as a higher percentage of patients with a satisfactory clinical response (39% vs. 29%; odds ratio, 1.56 95% CI, 1.05 to 2.32; P=0.03) and a greater improvement in the 6-minute walk distance (median change from baseline, 48.98 m vs. 23.80 m; P<0.001). The adverse events that occurred more frequently in the combination-therapy group than in either monotherapy group included peripheral edema, headache, nasal congestion, and anemia.
Among participants with pulmonary arterial hypertension who had not received previous treatment, initial combination therapy with ambrisentan and tadalafil resulted in a significantly lower risk of clinical-failure events than the risk with ambrisentan or tadalafil monotherapy. (Funded by Gilead Sciences and GlaxoSmithKline; AMBITION ClinicalTrials.gov number, NCT01178073.).
Cigarette smoking has been associated with alterations in the structure and endothelial function of pulmonary arteries. Nitric oxide (NO) and endothelin-1 are endothelium-derived mediators with ...opposite effects on vascular tone and cell growth. To investigate whether cigarette smoking could induce changes in the synthesis of these mediators in pulmonary arteries, we compared the expression of both endothelial NO synthase (eNOS) and endothelin-1 in the lungs of smokers with that in nonsmokers. Lung tissue samples of 23 smokers and nine nonsmokers were studied. Expression of eNOS and endothelin-1 in pulmonary artery endothelium was evaluated by immunohistochemistry. In protein extracts of lung tissue, the content of eNOS protein was assessed by Western blot analysis and that of endothelin-1 by radioimmunoassay. The immunohistochemical expression of eNOS in arterial endothelium and the eNOS protein content in lung tissue were lower in the smokers than in the nonsmokers. No differences were shown in cell expression and protein content of endothelin-1 between both groups. We conclude that cigarette smoking is associated with reduced expression of eNOS in pulmonary arteries. The diminished synthesis of nitric oxide may contribute to the alterations in the structure and endothelial function of pulmonary vessels in cigarette-smoke-induced respiratory disease.
AbstractBackground: Abnormalities of autonomic function have been reported in patients with chronic obstructive pulmonary disease. The effect of the exercise training in heart rate recovery (HRR) has ...not been established in patients with COPD. Objective: To assess the effects of 8-weeks' endurance training program on parasympathetic nervous system response measured as heart rate recovery in a sample of moderate-to-severe COPD patients. Methods: We recruited a consecutive sample of patients with COPD candidates to participate in a pulmonary rehabilitation program from respiratory outpatient clinics of a tertiary hospital. HRR was calculated, before and after training, as the difference in heart rate between end-exercise and one minute thereafter (HRR1) in a constant-work rate protocol. Results: A total of 73 COPD patients were included: mean (SD) age 66 (8) years, median (P25-P75) post-bronchodilator FEV1 39 (29-53)%. The prevalence of slow HRR1 (≤12 beats) at baseline was 63%, and was associated with spirometric severity (mean FEV1 35% in slow HRR1 vs 53 in normal HRR1, p < 0.001). After 8-weeks training, HRR1 improved from mean (SD) 10 (7) to 12 (7) beats (p = 0.0127). Multivariate linear regression models showed that the only variable related to post-training HRR1 was pre-training HRR1 (p < 0.001). Conclusions: These results suggest that training enhances HRR in patients with moderate-to-severe COPD. HRR is an easy tool to evaluate ANS such that it may be a useful clinical marker of parasympathetic nervous system response in patients with COPD.
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