Comorbidities and mortality in hypercapnic obese under domiciliary noninvasive ventilation.

BACKGROUND: The higher mortality rate in untreated patients with obesity-associated hypoventilation is a strong rationale for long-term noninvasive ventilation (NIV). The impacts of comorbidities, medications and NIV compliance on survival of these patients remain largely unexplored. METHODS: Observational cohort of hypercapnic obese patients initiated on NIV between March 2003 and July 2008. Survival curves were estimated by the Kaplan-Meier method. Anthropometric measurements, pulmonary function, blood gases, nocturnal SpO(2) indices, comorbidities, medications, conditions of NIV initiation and NIV compliance were used as covariates. Univariate and multivariate Cox models allowed to assess predictive factors of mortality. RESULTS: One hundred and seven patients (56% women), in whom NIV was initiated in acute (36%) or chronic conditions, were followed during 43±14 months. The 1, 2, 3 years survival rates were 99%, 94%, and 89%, respectively. In univariate analysis, death was associated with older age (>61 years), low FEV1 (<66% predicted value), male gender, BMI×time, concomitant COPD, NIV initiation in acute condition, use of inhaled corticosteroids, ß-blockers, nonthiazide diuretics, angiotensin-converting enzyme inhibitors and combination of cardiovascular drugs (one diuretic and at least one other cardiovascular agent). In multivariate analysis, combination of cardiovascular agents was the only factor independently associated with higher risk of death (HR = 5.3; 95% CI 1.18; 23.9). Female gender was associated with lower risk of death. CONCLUSION: Cardiovascular comorbidities represent the main factor predicting mortality in patient with obesity-associated hypoventilation treated by NIV. In this population, NIV should be associated with a combination of treatment modalities to reduce cardiovascular risk

Kaplan-Meier survival curves referring to BMI, gender, FEV1/VC, use of combination of cardiovascular agents and condition of NIV initiation.

<p>Kaplan-Meier survival curves referring to BMI, gender, FEV1/VC, use of combination of cardiovascular agents and condition of NIV initiation.</p

Follow-up data according to the condition of NIV initiation.

<p>Follow-up data according to the condition of NIV initiation.</p

Flow chart of the survey.

<p>CRF: Chronic Respiratory Failure; AHRF: Acute Hypercapnic Respiratory Failure; I.C.U: Intensive Care Unit.</p

Independent factors associated with risk of all-cause mortality (multivariate Cox model).

<p>Combination of cardiovascular agents: Combination of a diuretic and at least one other cardiovascular agent among ß-Blokers, Calcium antagonists, Converting Enzime Inhibitors, Antagiotensin II receptor blockers.</p

Baseline Characteristics according to NIV initiation conditions.

<p>Chronic = Chronic Respiratory Failure; Acute: Acute Respiratory Failure; I.C.U: Intensive Care Unit; BMI: Body Mass Index; n of ABG with O2: number of arterial blood gases realized with additional O_2; VC: Vital Capacity expressed as percentage of predicted value; FEV1/VC: Forced Expiratory Volume in one second/Vital Capacity ratio; Heart failure included (ischemic, hypertrophic or dilated); COPD: Chronic Obstructive Pulmonary Disease; OSAS: Obstructive Sleep Apnea Syndrome; CEI: Angiotensin Converting Enzyme Inhhnibitors; ARBs: Angiotensin II Receptor Blockers.</p>*<p>#: represent significant difference between pairwise comparisons.</p

Intravesical Ty21a Treatment of Non-muscle-invasive Bladder Cancer Shows a Good Safety Profile.

Standard-of-care immunotherapy for non-muscle-invasive bladder cancer (NMIBC) with intravesical Bacillus Calmettte-Guérin (BCG) is associated with adverse events (AEs), disease recurrence/progression, and supply shortages. Preclinical data have shown that intravesical instillation of Ty21a/Vivotif, the oral vaccine against typhoid fever, may be an effective and safer alternative to BCG. We assessed the safety of intravesical Ty21a in NMIBC. For ethical reasons, patients with low- or intermediate-risk NMIBC not requiring BCG immunotherapy were enrolled. To determine the maximum tolerated dose, escalating doses of Ty21a/Vivotif were intravesically instilled in three patients once a week for 4 wk in phase 1a. In phase 1b, ten patients received the selected dose (1 × 10 &lt;sup&gt;8&lt;/sup&gt; CFU) once a week for 6 wk, as for standard BCG therapy. At this dose, all patients completed their treatment. Most patients experienced minor systemic AEs, while half reported mild local bladder AEs. AEs only occurred after one or two instillations for 40% of the patients. Ty21a bacteria were only recovered in three out of 72 urinary samples at 1 wk after instillation. Intravesical Ty21a might be well tolerated with no cumulative side effects, no fever &gt;39 °C, and lower risk of bacterial persistence than with BCG. Ty21a treatment thus warrants clinical trials to explore its safety and antitumor efficacy in high-risk NMIBC. This trial is registered on ClinicalTrials.gov as NCT03421236. We examined the safety of a new intra-bladder immunotherapy for non-muscle-invasive bladder cancer as an alternative to the standard BCG treatment. Our data show that the Ty21a vaccine might be well tolerated. Further studies are needed to determine the safety and antitumor efficacy of this treatment

Response to Statin Therapy in Obstructive Sleep Apnea Syndrome: A Multicenter Randomized Controlled Trial

Rationale. Accumulated evidence implicates sympathetic activation as inducing oxidative stress and systemic inflammation, which in turn lead to hypertension, endothelial dysfunction, and atherosclerosis in obstructive sleep apnea (OSA). Statins through their pleiotropic properties may modify inflammation, lipid profile, and cardiovascular outcomes in OSA. Methods. This multicenter, randomized, double-blind study compared the effects of atorvastatin 40 mg/day versus placebo over 12 weeks on endothelial function (the primary endpoint) measured by peripheral arterial tone (PAT). Secondary endpoints included office blood pressure (BP), early carotid atherosclerosis, arterial stiffness measured by pulse wave velocity (PWV), and metabolic parameters. Results. 51 severe OSA patients were randomized. Key demographics for the study population were age 54 ± 11 years, 21.6% female, and BMI 28.5 ± 4.5 kg/m2. In intention to treat analysis, mean PAT difference between atorvastatin and placebo groups was 0.008 (−0.29; 0.28), P=0.979. Total and LDL cholesterol significantly improved with atorvastatin. Systolic BP significantly decreased with atorvastatin (mean difference: −6.34 mmHg (−12.68; −0.01), P=0.050) whereas carotid atherosclerosis and PWV were unchanged compared to the placebo group. Conclusion. In OSA patients, 3 months of atorvastatin neither improved endothelial function nor reduced early signs of atherosclerosis although it lowered blood pressure and improved lipid profile. This trial is registered with NCT00669695

Response to Statin Therapy in Obstructive Sleep Apnea Syndrome: A Multicenter Randomized Controlled Trial

Rationale. Accumulated evidence implicates sympathetic activation as inducing oxidative stress and systemic inflammation, which in turn lead to hypertension, endothelial dysfunction, and atherosclerosis in obstructive sleep apnea (OSA). Statins through their pleiotropic properties may modify inflammation, lipid profile, and cardiovascular outcomes in OSA. Methods. This multicenter, randomized, double-blind study compared the effects of atorvastatin 40 mg/day versus placebo over 12 weeks on endothelial function (the primary endpoint) measured by peripheral arterial tone (PAT). Secondary endpoints included office blood pressure (BP), early carotid atherosclerosis, arterial stiffness measured by pulse wave velocity (PWV), and metabolic parameters. Results. 51 severe OSA patients were randomized. Key demographics for the study population were age 54 ± 11 years, 21.6% female, and BMI 28.5 ± 4.5 kg/m 2 . In intention to treat analysis, mean PAT difference between atorvastatin and placebo groups was 0.008 (−0.29; 0.28), = 0.979. Total and LDL cholesterol significantly improved with atorvastatin. Systolic BP significantly decreased with atorvastatin (mean difference: −6.34 mmHg (−12.68; −0.01), = 0.050) whereas carotid atherosclerosis and PWV were unchanged compared to the placebo group. Conclusion. In OSA patients, 3 months of atorvastatin neither improved endothelial function nor reduced early signs of atherosclerosis although it lowered blood pressure and improved lipid profile. This trial is registered with NCT00669695