The relationship between adherence, antiretroviral regimen, and viral load (VL) suppression was assessed through a 1 year prospective follow-up study among 1142 HIV-infected patient. Patients on antiretroviral therapy who attended to the pharmacy during a 6-month period were considered eligible. Those included in the final analysis were patients who had been taking the same antiretroviral therapy for > or =6 months since their inclusion. The cohort included patients taking first line therapy (n = 243) and antiretroviral-experienced patients (n = 899). Naive patients who were included had to have reached undetectable VL at enrollment. Antiretroviral-experienced patients with detectable VL determinations in the previous 6 months were excluded. Adherence was measured by means of announced pill counts and dispensation pharmacy records. Of patients, 58% were taking NNRTI, 31.4% boosted PI, and 10.6% unboosted PI-based regimens. Overall, the relative risk of virologic failure was 9.0 (95% CI 4.0-20.1) in patients with adherence 80-89.9%, 45.6 (95% CI 19.9-104.5) with adherence 70-79.9%, and 77.3 (95% CI 34.2-174.9) with adherence <70%, compared with adherence of > or =90%. The risk of virologic failure in patients with adherence <90% taking unboosted PI was 2.5 times higher than the group taking boosted PI (95% CI 1.2-5.3). There were no statistical differences in patients taking boosted PI and those who were taking NNRTI. Less than 95% of adherence is associated with high virologic success. For patients taking NNRTI- or boosted PI-based regimens with adherence rates of 80%, the failure rate is <10%. These data do not affect the goal of achieving the highest level of adherence possible.

Patients with idiopathic pulmonary fibrosis (IPF) usually develop hypoxemia and pulmonary hypertension when exercising. To what extent endothelium-derived vasodilating agents modify these changes is unknown. The study was aimed to investigate in patients with IPF whether exercise induces changes in plasma levels of endothelium-derived signaling mediators, and to assess the acute effects of inhaled nitric oxide (NO) on pulmonary hemodynamics and gas exchange, at rest and during exercise. We evaluated seven patients with IPF (6 men/1 woman; 57 ± 11 yr; forced vital capacity, 60 ± 13% predicted; carbon monoxide diffusing capacity, 52 ± 10% predicted). Levels of endothelin, 6-keto-prostaglandin-F1α, thromboxane B2, and nitrates were measured at rest and during submaximal exercise. Pulmonary hemodynamics and gas exchange, including ventilation-perfusion relationships, were assessed breathing ambient air and 40 ppm NO, both at rest and during submaximal exercise. The concentration of thromboxane B2 increased during exercise ( P = 0.046), whereas levels of other mediators did not change. The change in 6-keto-prostaglandin-F1α correlated with that of mean pulmonary arterial pressure ( r = 0.94; P < 0.005). Inhaled NO reduced mean pulmonary arterial pressure at rest (−4.6 ± 2.1 mmHg) and during exercise (−11.7 ± 7.1 mmHg) ( P = 0.001 and P = 0.004, respectively), without altering arterial oxygenation or ventilation-perfusion distributions in any of the study conditions. Alveolar-to-capillary oxygen diffusion limitation, which accounted for the decrease of arterial Po2 during exercise, was not modified by NO administration. We conclude that, in IPF, some endothelium-derived signaling molecules may modulate the development of pulmonary hypertension during exercise, and that the administration of inhaled NO reduces pulmonary vascular resistance without disturbing gas exchange.

Surgery alone or in combination with other strategies gives the best hope for lung survival in patients with resectable nonsmall-cell lung cancer [1]. Most patients with lung cancer are current smokers or exsmokers and often have associated chronic obstructive pulmonary disease (COPD) [2] and other comorbidity factors that increase the risk of postoperative complications and death. Pulmonary function tests (PFT) and split pulmonary function, as determined by quantitative macroaggregate lung scanning, are useful in identifying patients with impaired lung function who are at risk of postoperative complications [3]. To what extent further functional testing contributes to more accurate prediction of postoperative morbidity and mortality is unclear.Some authors have recommended exercise testing as a useful tool in the assessment of operative risk in thoracotomy candidates [4,5]. Impaired exercise capacity, as assessed by a low oxygen uptake (V 'O 2 ), has been proposed as a predictor of a poor postoperative outcome [4], but the usefulness of V 'O 2 imeasurements in patients with severely impaired pulmonary function at increased risk remains controversial. While some authors have shown that the V 'O 2 value is useful in the prediction of surgical outcome in high-risk candidates [6-9], others have not confirmed such results [10,11].Furthermore, since pulmonary hypertension is a poor prognostic factor in COPD [12] and a decreased arterial O 2 saturation on exertion has been proposed as a predictor of postoperative complications [13,14], it was hypothesized that among COPD patients who are at a high-risk for resectional lung surgery, those who develop gas exchange and/or haemodynamic abnormalities during exercise may be at greatest risk of morbidity and mortality after surgery. Accordingly, the present study was intended to evaluate the potential role of both gas exchange and pulmonary haemodynamic measurements during exercise in the prediction of early post-thoracotomy morbidity and mortality in patients with a high-risk for surgery as assessed by conventional PFT and lung scanning. Invasive exercise testing in the evaluation of patients at high-risk for lung resection. J. Ribas, O. Díaz, J.A. Barberà, M. Mateu, E. Canalís, L. Jover, J. Roca, R. Rodriguez-Roisin. ©ERS Journals Ltd 1998.ABSTRACT: The aim of this study was to investigate whether invasive exercise testing with gas exchange and pulmonary haemodynamic measurements could contribute to the preoperative assessment of patients with lung cancer at a high-risk for lung resection.Sixty-five patients scheduled for thoracotomy (aged 66±8 yrs (mean±SD), 64 males, forced expiratory volume in one second (FEV1) 54±13% predicted) were studied prospectively. High risk was defined on the basis of predicted postpneumonectomy (PPN) FEV1 and/or carbon monoxide diffusing capacity of the lung (DL,CO) <40% pred. Arterial blood gas measurements were performed in all patients at rest and during exercise. In 46 patients, pulmonary haemodynamic measurements were also performed at re...

BackgroundA subclinical left ventricle diastolic dysfunction (LVDD) has been described in patients with chronic obstructive pulmonary disease (COPD).ObjectivesTo evaluate the prevalence of LVDD in stable severe COPD patients, to analyze its relationship with exercise capacity and to look for its possible causes (lung hyperinflation, ventricular interdependence or inflammatory mechanisms).MethodsWe evaluated 106 consecutive outpatients with severe COPD (FEV1 between 30–50%). Thirty-three (31%) were excluded because of previous heart disease. A pulmonary function test, a 6-minute walking test (6MWT), a Doppler echocardiography test, including diastolic dysfunction parameters, and an analysis of arterial blood gases, NT-proBNP and serum inflammatory markers (CRP, leucocytes), were performed in all patients.ResultsThe prevalence of LVDD in severe stable COPD patients was 90% (80% type I, n=57, and 10% type II, n=7). A significant association between a lower E/A ratio (higher LVDD type I) and a lower exercise tolerance (6-minute walked distance (6MWD)) was found (r=0.29, p<0.05). The fully adjusted multivariable linear regression model demonstrated that a lower E/A ratio, a DLCO in the quartile 4th and a higher tobacco consumption were associated with a lower 6MWD (76, 57 and 0.7 metres, respectively, p<0.05). A significant correlation between E/A ratio and PaO2 was observed (r=0.26, p<0.05), but not with static lung hyperinflation, inflammation or right ventricle overload parameters.ConclusionIn stable severe COPD patients, the prevalence of LVDD is high and this condition might contribute in their lower exercise tolerance. Hypoxemia could have a concomitant role in their pathogenesis.

The goal of this study was to build a population pharmacokinetic (PK) model to characterize the population PK parameters in our hospitalized patients. Teicoplanin serum concentrations from clinical routine were used. Antibiotic dose history and blood collection times were recorded and analyzed with NONMEM-V. Demographic and biologic data creatinine clearance (CLcr), weight (WT), and albumin (Alb) were tested for inclusion as covariates in the basic model. Intraindividual and residual variability were modeled. One hundred seven sparse samples (mainly trough levels), from 79 patients, were included. A 2-compartment PK model characterized by clearance (CL), central compartment volume of distribution (Vc), intercompartment clearance, and steady-state volume of distribution (VSS) with first-order elimination adequately described the data. CLcr and WT significantly influenced teicoplanin CL (CL = 0.57[0.15]*(1+0.0048[0.39]*(CLcr - averageCLcr)*WT) L/h). VSS was not affected by any covariate (VSS = 50.2[0.13]L). A negative trend between Alb and individual VSS estimates was observed without statistical significance. In a new data set, bias and precision resulted in mean values of -3.24% and 9.42%, respectively. In conclusion, CLcr and WT are significant covariates on teicoplanin CL. Results from predictive accuracy and precision show the usefulness of this model for implementation in a therapeutic drug monitoring program in the near future.

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Background: Gender differences in organ involvement and clinical severity have been poorly described in hereditary hemorrhagic telangiectasia (HHT). The aim of this study was to describe differences in the severity of HHT manifestations according to gender. Methods: Severity was measured according to Epistaxis Severity Score (ESS), Simple Clinical Scoring Index for hepatic involvement, a general HHT-score, needing for invasive treatment (pulmonary or brain arteriovenous malformations-AVMs-embolization, liver transplantation or Young's surgery) or the presence of adverse outcomes (severe anemia, emergency department-ED-or hospital admissions and mortality). Results: One hundred forty-two (58.7%) women and 100 (41.3%) men were included with a mean age of 48.9 ± 16.6 and 49 ± 16.5 years, respectively. Women presented hepatic manifestations (7.1% vs 0%) and hepatic involvement (59.8% vs 47%), hepatic AVMs (28.2% vs 13%) and bile duct dilatation (4.9% vs 0%) at abdominal CT, and pulmonary AVMs at thoracic CT (35.2% vs 23%) more often than men. The Simple Clinical Scoring Index was higher in women (3.38 ± 1.2 vs 2.03 ± 1.2), and more men were considered at low risk of harboring clinically significant liver disease than women (61% vs 25.3%). These differences were mantained when considering HHT1 and HHT2 patients separetely. Duodenal telangiectasia were more frequent in men than women (21% vs 9.8%). Invasive treatments were more frequently needed in women (28.2% vs 16%) but men needed attention at the ED more often than women (48% vs 28.2%), with no differences in ESS, HHT-score, anemia hospital admissions or mortality. Conclusions: HHT women showed more severe hepatic involvement than men, also among HHT1 and HHT2 patients. Women had higher prevalence of pulmonary AVMs and needed invasive procedures more frequently, while men needed attention at the ED more often. These data might help physicians to individualize HHT patients follow-up.