The effectiveness of a bronchial drainage technique (ELTGOL) in COPD exacerbations

Background and objective:   Exacerbations of COPD are often characterized by increased mucus production that is difficult to treat and worsens patients' outcome. This study evaluated the efficacy of a chest physiotherapy technique (expiration with the glottis open in the lateral posture, ELTGOL) during acute exacerbations of COPD using as outcome measures sputum volume, length of hospitalization, reduction in dyspnoea (Borg score), improvement in quality of life (assessed by the St George Respiratory Questionnaire) and incidence of COPD exacerbations during follow up.
Methods:   The study recruited 59 patients hospitalized for the treatment of acute exacerbation of COPD, who were randomly assigned to a control group and an intervention group. The control group was treated with standard medical therapy while the intervention group was treated with ELTGOL plus medical therapy. A subgroup of patients was followed for 6 months to verify the effects on COPD exacerbations and need for hospitalizations.
Results:   At the time of hospital discharge there was no significant difference between the two groups in the outcome measures, with the exception of the Borg score, which was significantly improved in the ELTGOL group (4.3 ± 1.5 in the control group vs 3.0 ± 1.8 in the ELTGOL group, P  = 0.004). After 6 months there was no significant difference in the other measured parameters between a subset of the groups available for follow up. During follow up, the ELTGOL group had numerically fewer exacerbations and less need for hospitalization though differences were not statistically significant.
Conclusions:   Chest physiotherapy using the ELTGOL technique has a limited role in patients with mild exacerbation of moderate to severe COPD with a tendency towards fewer exacerbations and hospitalizations.     

Predictors of delay in the diagnosis and clinical trial entry of amyotrophic lateral sclerosis patients: a population-based study

BACKGROUND: The El Escorial and the revised Airlie House diagnostic criteria for amyotrophic lateral sclerosis (ALS) were introduced to select patients for clinical trials. Heterogeneity of clinical presentation at onset and delay in diagnosis may decrease the likelihood for trial entry. OBJECTIVE: Identify risk factors for delay in the diagnosis and trial exclusion. METHODS: ALS incident cases were identified with El Escorial (EEC) and Airlie House criteria (AHC) through a population-based registry established in Puglia, Southern Italy, in the years 1998-99. RESULTS: 130 ALS incident cases were diagnosed with a median interval between onset of symptoms and diagnosis of 9.3 months and not different across both EEC and AHC categories. Twenty percent of cases were not eligible for clinical trials according to the AHC. About 5% of subjects in this series died with only lower motor neuron signs. Predictors for delay in the diagnosis were age between 65 and 75 years and spinal onset while fasciculations and cramps as first symptoms were predictors of exclusion from trials. CONCLUSIONS: In this population-based series, diagnostic delay was longer in subjects with spinal onset and age between 65 and 75 and fasciculation as first symptoms. About 80% of incident cases were trial eligible with AHC criteria. However, a significant number of subjects with ALS, characterized by a limited spread of signs, were not trial eligible while alive.     

Nonsteroidal anti-inflammatory drugs and the incidence of Parkinson disease

Animal and epidemiologic studies suggest that nonsteroidal anti-inflammatory drugs (NSAIDs) decrease the incidence of Parkinson disease (PD). The authors studied 1,258 PD cases and 6,638 controls from the General Practice Research Database. The odds ratios (95% CI) for ever vs never use were 0.93 (0.80 to 1.08) for nonaspirin NSAIDs, 1.29 (1.05 to 1.58) for aspirin, and 1.16 (1.00 to 1.35) for acetaminophen. Nonaspirin NSAID use was associated with a higher risk in women and a lower risk in men.     

Motor evoked potentials in a mouse model of chronic multiple sclerosis

We tested cortical motor evoked potentials (cMEPs) as a quantitative marker for in vivo monitoring of corticospinal tract damage in a murine multiple sclerosis model (experimental autoimmune encephalomyelitis, EAE). The cMEPs, previously standardized in naive C57BL/6 developing and adult mice, were studied longitudinally in adult EAE mice. Central conduction times (CCTs) increased significantly shortly before the earliest clinical signs developed (10 days postimmunization, dpi), with peak delay in acute EAE (20-40 dpi). In clinically stable disease (80 dpi), CCTs did not increase further, but cMEP amplitude declined progressively, with complete loss in >80% of mice at 120 dpi. Increase in CCT correlated with presence of inflammatory infiltrates and demyelination in acute EAE, whereas small or absent cMEPs were associated with continuing axonal damage in clinically-stabilized disease and beyond (>80 dpi). These results demonstrate that cMEPs are a useful method for monitoring corticospinal tract function in chronic-progressive EAE, and provide insight into the pathological substrate of the condition.     

Role of fibrinolysis and interventional therapy for acute venous thromboembolism

The initial goals of treatment for venous thromboembolism (VTE) are usually achieved with anticoagulation. This review focuses on fibrinolysis and interventional therapy in VTE, treatments whose indications are much more controversial. The benefit-to-risk ratio of fibrinolysis in deep vein thrombosis (DVT) is dubious. Thrombolytic treatment is recommended for unstable patients with pulmonary embolism (PE), although these patients represent less than 5% of all patients hospitalized for PE. The use of thrombolytic treatment in patients with sub-massive PE remains controversial. Two indications are widely recognized for inferior vena cava filters: the first is a permanent or temporary contraindication to anticoagulation, in patients with proximal DVT or PE. The second is the occurrence of PE or propagation of the thrombus in patients treated for DVT or recurrence in patients with PE. The PREPIC study demonstrated that in acute VTE, vena cava filters reduced the risk of PE but increased that of DVT and had no effect on survival. The fact that prevention of PE is mainly observed during the short initial period following the diagnosis of an acute VTE event justifies a new randomized study with the use of retrievable filters as an adjuvant to anticoagulation in high risk patients with PE.     

Brain transcranial direct current stimulation modulates motor excitability in mice

Shortly after the application of weak transcranial direct current stimulation (tDCS) to the animal and human brain, changes in corticospinal excitability, which mainly depend on polarity, duration and current density of the stimulation protocol, have been reported. In humans, anodal tDCS has been reported to enhance motor‐evoked potentials (MEPs) elicited by transcranial brain stimulation while cathodal tDCS has been shown to decrease them. Here we investigated the effects produced by tDCS on mice motor cortex. MEPs evoked by transcranial electric stimulation were recorded from forelimbs of 12 C57BL/6 mice, under sevofluorane anaesthesia, before and after (0, 5 and 10 min) anodal and cathodal tDCS (tDCS duration 10 min). With respect to sham condition stimulation (anaesthesia), MEP size was significantly increased immediately after anodal tDCS, and was reduced after cathodal tDCS (～20% vs. sham). Both effects declined towards basal levels in the following 10 min. Although the site and mechanisms of action of tDCS need to be more clearly identified, the directionality of effects of tDCS on mice MEPs is consistent with previous findings in humans. The feasibility of tDCS in mice suggests the potential applicability of this technique to assess the potential therapeutic options of brain polarization in animal models of neurological and neuropsychiatric diseases.     

Bosentan for chronic thromboembolic pulmonary hypertension: Findings from a systematic review and meta-analysis

Background

After acute pulmonary embolism, chronic thromboembolic pulmonary hypertension (CTEPH) is diagnosed in about 1% of patients. We performed a systematic review and meta-analysis aimed at assessing the effects of bosentan therapy in patients with CTEPH.

Methods

We searched in MEDLINE and Embase using the terms ‘pulmonary hypertension’ AND ‘bosentan’. Papers were included in this review if they reported on patients with objectively confirmed CTEPH treated with bosentan. Efficacy measures were the improvement in NYHA class, in 6 minute walking distance (6mwd) and in hemodynamics (cardiac index, pulmonary artery pressure, pulmonary vascular resistance). Mortality and safety were also assessed.

Results

Overall, 543 papers were found. Eight single-arm cohort studies (175 patients), one randomized double-blind study, one case-control study and one case report were included in the analysis.A 35.9 meters weighted mean increase in 6 minute walking distance was observed after 3-6 months of treatment (9 studies, 208 patients) (95% CI 33.6 to 38.2; p < 0.001) and an additional increase of 21 meters after one year (4 studies, 80 patients). About 25% of patients had an improvement on functional NYHA class at 3-6 months. Data on hemodynamics were available in seven studies, 185 patients. The mean weighted increase in cardiac index at 3-6 months was 0.23 l/min/m2 (95% CI 0.22 to 0.25); the mean weighted decrease in pulmonary artery pressure at 3-6 months was 2.62 mmHg (95% CI 2.44 to 2.80). Three patient died within 3-6 months (1.4%) and 3 additional patients died within one year.

Conclusions

Bosentan therapy is associated with an improvement of hemodynamics and probably exercise capacity in patients with CTEPH. Controlled data on mortality and time to clinical worsening in patients with CTEPH are needed.     

Bolus tenecteplase for right ventricle dysfunction in hemodynamically stable patients with pulmonary embolism

Introduction

The clinical benefit of thrombolytic treatment over heparin in patients with pulmonary embolism without hemodynamic compromise remains controversial. In these patients bolus tenecteplase has the potential to provide an effective and safe thrombolysis.

Methods

We evaluated the effect of tenecteplase on right ventricle dysfunction (RVD) assessed by echocardiography in hemodynamically stable patients with PE in a multicenter, randomized, double-blind, placebo-controlled study. RVD was defined as right/left ventricle end-diastolic dimension ratio > 1 in the apical 4-chamber view. Patients were randomized to receive weight-adjusted single-bolus tenecteplase or placebo. All patients received unfractionated heparin. Reduction of RVD at 24 hours was the primary efficacy end-point and was evaluated by an independent committee unaware of treatment allocation.

Results

Overall, 58 patients were randomized. Echocardiograms were adequate for efficacy analysis in 51 patients, 23 randomized to tenecteplase and 28 to placebo. The reduction of right to left ventricle end-diastolic dimension ratio at 24 hours was 0.31 ± 0.08 in patients randomized to tenecteplase as compared to 0.10 ± 0.07 in patients randomized to placebo (p = 0.04). One patient randomized to tenecteplase suffered a clinical event (recurrent pulmonary embolism) in comparison to three patients randomized to placebo (1 recurrent pulmonary embolism; 1 clinical deterioration and 1 non pulmonary embolism-related death). Two non fatal major bleedings occurred with tenecteplase (1 intracranial) and one with placebo.

Conclusion

In hemodynamically stable patients with PE, treatment with single bolus tenecteplase is feasible at the same dosages used for acute myocardial infarction and is associated with reduction of RVD at 24 hours. Whether this benefit is associated with an improved clinical outcome without excessive bleeding is currently explored in a large clinical trial.