Reviews on Recent Clinical Trials - Volume 5, Issue 2, 2010

During the 80' and the 90's, the role of pulmonary rehabilitation (PR) was still not clearly demonstrated. The following development of PR was mainly due to the increasing number of clinical studies providing proofs of its effectiveness, and convincing physicians, institutions, and regulatory agencies about its additional value to conventional pharmacological therapies. In the later years, PR has become an evidence-based non pharmacological treatment, designed for patients suffering from chronic obstructive lung disease (COPD). In the pulmonary rehabilitation programs (PRPs), exercise is essential for improving muscular tone and thus reducing disability. This later is due to chronic breathlessness, fatigue, and impairment of daily activities, that cause a reduction in functional performance and quality of life (QoL) in COPD patients. PRPs include also educational, psychosocial and nutritional interventions, so that it becomes a multifaceted approach. Despite the existing consciousness that PR results in improvement of exercise tolerance, dyspnea, and QoL, it is prescribed by most health professionals, and only about 2% of COPD patients undergo PRPs. An appropriate consideration of the PR is essential to ensure optimal management of COPD, in particular when patients have respiratory symptoms that lead to a decrease in physical activity.

Although standard anticoagulation, including heparins and vitamin K antagonists (VKA), is clinically beneficial, several unmet needs remain due to several pharmacokinetic and pharmacodymamic limitations. Selective anticoagulant agents have been developed to overcome the drawbacks associated with both heparins and.VKA. Agents selectively targeting factor Xa, IXa and thrombin are alternative anticoagulants in the most advanced phases of clinical development. Compared to traditional anticoagulants these drugs have the potential to be more effective, safer and easier to use and to provide a more predictable dose response, without need for routine monitoring and dose adjustment. This review will summarize the current status of selective anticoagulant drugs, which are already licensed or being evaluated in advanced phases clinical studies for antithrombotic treatment in non-valvular atrial fibrillation, percutaneous coronary intervention and acute coronary syndromes, focusing on design and results of studies in these specific clinical settings.

Stress echocardiography is a useful tool for the clinical decision making process, given its accuracy and demonstrated prognostic value. Among available stress echocardiography techniques, exercise is safer and more physiologic, therefore it must be considered the first choice for patients able to exercise. Peak exercise echocardiography has greater sensitivity than post-exercise imaging. Image quality of apical views at peak exercise is similar than that of images acquired during the immediate post-exercise period. Although more demanding than post-exercise treadmill imaging, the successfulness of peak treadmill exercise imaging may be improved with some skills. The role of new technology is promising for exercise echo. Doppler tissue and speckle imaging can assess myocardial velocities and deformation. However, although Doppler tissue imaging increases the agreement and accuracy among novel readers, it has not been demonstrated to be better than visual assessment when the latter is performed by experienced observers. Speckle imaging can easily measure myocardial torsion, which has been found to be altered under ischemic conditions. Finally, 3-dimensional echocardiography can also be used during exercise since a full volume of the entire myocardium can be obtained in a few cardiac cycles.

Hypofractionated irradiation has an established role in the palliative treatment of patients with advanced medically inoperable non - small cell lung cancer (NSCLC) and poor performance status. Also hypofractionated radiotherapy merits careful consideration in the curative treatment of patients with Stage I and II disease using contemporary technology. The biological effect of radiation on tumours is increased as the overall treatment time is shortened. Hypofractionated field radiotherapy offers acceptable palliation with minimal toxicity. The rates of palliation for hemoptysis, chest pain, cough and dyspnea reported from studies with very short regimen (8,5 Gy x 2), are comparable to those of other trials that used more protracted palliative treatment. The observed toxicity is minimal, and no cases of oesophagitis, pneumonitis, or radiation myelopathy developed. The minimal toxicity is a reflection of both the low biologic total dose and the tight RT design. Therefore the radiation side effects appear to be related to the technique of RT delivered rather than the patient's PS. Hence, widely believed dogmas concerning the tolerance of critical structures to conventionally fractionated doses, such as the dose-volume effect, total dose, and time (latency) dependency, has to be re-evaluated for hypofractionated radiation therapy. As well there is data suggesting that the small stages I — II NSCLC are likely to benefit from hypofractionated regimens too. Hypofractionated stereotactic radiotherapy is a new technically complex approach to the treatment of early-stage nonsmall cell lung cancer. It is capable to deliver much higher doses to the cancer than is possible with standard techniques, and as a result, rates of tumour control are high and similar to what can be achieved by surgical resection. Refinements of technique and dose as well as randomized data are required before stereotactic radiotherapy can be endorsed as a standard of care for patients with inoperable peripherally located T1 non small cell lung cancer. A clear advantage of the very short hypofractionated palliative regimen is that it allows patients with a short expected survival time to spend more of their remaining time away from the hospital.

Photodynamic therapy (PDT) with methylaminolevulinate (MAL) has demonstrated high efficacy, minimal side effects, and improved cosmetic outcome in the treatment of its EU-approved clinical indications, i.e. actinic keratoses (AKs), basal cell carcinoma, and Bowen's disease. In addition, PDT with MAL or 5-aminolevulinic acid (ALA) is approved in the US for the treatment of AK. However, besides anti-tumoral activity, PDT has also demonstrated various anti-inflammatory and anti-infectious effects as well as those on the metabolism of connective tissue, keratinization of normal keratinocytes and maturation processes of sebaceous glands and hair follicles. These findings have expanded the spectrum of possible applications of PDT that now encompasses infectious (viral, bacterial, fungal, protozoal) disorders, epidermal and dermal inflammatory diseases, tumors of lymphocytes, adnexal diseases and premature skin aging due to sun exposure. However, the findings obtained so far must be considered in most off-label indications only preliminary and more detailed studies are required to clarify the role of PDT beyond the treatment of non-melanoma skin cancer. In addition, possible advantages over standard treatments remain to be clarified.

Malignant solid tumors have been traditionally treated utilizing cytotoxic chemotherapies, which work against rapidly multiplying tumors. The current response evaluation in solid tumor is based on the Response Evaluation Criteria in Solid Tumors (RECIST). This method relies mainly on computerized tomography (CT scans) and other imaging modalities by which the diameter of tumors is taken into consideration to assess response to therapy. Recent years have witnessed the introduction of a series of new signal transduction inhibitors in the management of metastatic RCC. Stable disease (SD) is more frequently seen with morphologic lesion changes such as, change in attenuation, pattern of intratumoral enhancement / necrosis and cavitation, all of which pose a challenge for the investigator in the accurate assessment of response to therapy. This article attempts to introduce the reader to various alternate concepts of monitoring response following biologic therapy and offers a detailed analysis of a few lesions.

Adenoidal hypertrophy is probably the most frequent pathology in the pediatric population. This disorder manifests with several symptoms such as bilateral nasal obstruction, rhinorrhea, cough, snoring, hyponasal speech, hypopnea, and sleep apnea. When tonsillar hypertrophy is also present, obstructive sleep apnea syndrome can manifest. To date, nasal endoscopic examination is the standard technique to diagnose and estimate adenoid mass. Adenotomy is considered the surgical treatment of choice to resolve nasopharyngeal obstruction due to adenoidal hypertrophy. At present, several pitfalls of adenotomy (i.e., alteration of the immunological system, postoperative bleeding, and recurrence of adenoids) are object of criticism. For this reason, some researchers have tested the efficacy of topical nasal steroids in decreasing the severity of nasal symptoms and adenoidal mass. Herein, we review the literature on conservative treatments including also our personal experience.

The no — reflow phenomenon occurs in one third of the patients treated with primary percutanous intervention for acute ST segment elevation myocardial infarction. In addition of the effect of prolonged ischaemia, also reperfusion injury contributes significantly to the microvascular damage in the perfusion territory of the infarct — related coronary artery. In the recent years there has been an increasing interest in the concept of adjunctive mechanical thrombectomy to improve outcomes in primary percutaneous coronary intervention. In the literature randomized trials of thrombectomy have provided conflicting results with no definitive evidence for efficacy. The recently published Thrombus Aspiration During Percutaneous Coronary Intervention in Acute Myocardial Infarction Study (the largest randomized study of a thrombectomy device) demonstrates that adjunctive treatment with aspiration and manual thrombectomy improves clinical end — point. The aim of the report is to review the evidence to our date on the role of mechanical thrombectomy during primary percutaneous intervention in the setting of acute myocardial infarction.