Reviews on Recent Clinical Trials - Volume 8, Issue 1, 2013

Attention deficit hyperactivity disorder (ADHD) is a common psychiatric disorder in children and adolescents. Stimulants are commonly prescribed for ADHD management. There is clinical trial evidence that some medications with noradrenergic properties such as atomoxetine are effective. It is of theoretical and practical importance if other agents with noradrenergic properties display a comparable pattern of efficacy. This paper is a systematic review of the efficacy and safety of venlafaxine for treating children and adolescents with ADHD. MEDLINE, Google scholar, Scopus, and Web of science (ISI) databases were electronically searched in July 2012, updated on November 2012. Time and language of publication were not exclusion criteria. Efficacy outcomes were assessed by a valid and reliable parent- and/or teacher-reported instrument to evaluate clinical symptoms. Adverse effects were also evaluated. There were three uncontrolled trials and only two double blind controlled clinical trials. Venlafaxine appeared effective for treating ADHD. The rates of some adverse effects of venlafaxine were less than those documented for methylphenidate. While one of the two small controlled trials did not find difference between venlafaxine ad methylphenidate, the other trial reported lower efficacy for venlafaxine. Headache, insomnia, and nausea were among the most common adverse effects. This systematic review provides preliminary support that venlafaxine may have short term utility in treating ADHD in children and adolescents. However, before recommending venlafaxine for treatment, more robust and larger clinical trials, in particular providing evidence of its long-term efficacy, safety and tolerability are required.

Irritable bowel syndrome (IBS) is one of the most common gastrointestinal disorders and it is characterized by episodes of abdominal pain and altered bowel functions. The specific bowel disturbances of diarrhea, constipation or an alternation between the two defines the IBS subtypes of diarrhea-predominant, constipation-predominant, and mixed or alternating IBS. Because of the abnormalities in bowel states associated with each IBS subtype, it is not likely that one agent would successfully treat all three subtypes. As a result, clinical trials have focused, for the most part, on one IBS subtype. Over the past 2 decades very few agents have achieved regulatory approval for the treatment of IBS. In the present article we review publications reporting on phase 2 and phase 3 studies evaluating agents to potentially be used in the treatment of patients with IBS.

The search for new agents and for innovative strategies is warranted in the treatment of advanced non small cell lung cancer (NSCLC) because the outcomes remain unsatisfactory for most patients. Maintenance treatment with either a chemotherapeutic agent or a molecularly targeted agent after first-line chemotherapy is a very interesting strategy that has been largely investigated in the last years. Maintenance treatment can consist of drugs included in the induction regimen (continuation maintenance) or other non–cross-resistant agents not included in the induction regimen (switch maintenance). The switch maintenance strategy with the Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor erlotinib (in all the histologies) or with pemetrexed (in non-squamous histologies) have been demonstrated to be two possible effective options versus the classic break from cytotoxic chemotherapy after a fixed course in the treatment of advanced NSCLC. However some biases may have influenced the outcomes of switch maintenance trials as the low rate of patients treated with erlotinib and pemetrexed in the placebo arms. Very recently, a randomized phase III trial named PARAMOUNT has demonstrated a clinically significant benefit in overall survival with a good safety profile versus placebo in favour of continuation maintenance with pemetrexed after four cycles of induction with cisplatin plus pemetrexed. Continuation maintenance can be considered the true maintenance strategy because switch maintenance is an early second-line treatment. Continuation maintenance with pemetrexed after cisplatin plus pemetrexed induction for patients selected for a maintenance strategy is recommended as first-line treatment of advanced non-squamous NSCLC.

Manufacturers of consumer products consistently seek to improve marketed products in terms of both safety and efficacy. The desire for continued improvement is seen even in well-established products such as catamenial products which have existed in some form for thousands of years. A recent innovation in the design of menstrual pads is the addition of a surface finish of emollient for the purpose of increasing comfort during wear. The present paper presents different evaluations of such an emollient-treated menstrual pad with a novel absorbent core. These investigations demonstrated product tolerability, defined the optimal formulation and concentration of the emollient-containing finish, and demonstrated successful transfer of the emollient to the relevant skin surface. In addition, enhancement of skin moisturization, associated with exposure to the emollient-treated pad, was demonstrated by several technologies: assessment of skin moisturization by Corneometer®, skin friction testing, and skin capacitance.

Male Stress Urinary Incontinence (SUI) is an increasingly recognized problem particularly after the treatment of prostate cancer. Postprostatectomy incontinence is a major problem that needs to be solved, since it has great impact on quality of life affecting the patient’s physical activity and social well-being. The initial treatment for SUI that persists after 12 months consists of conservative measures such as pelvic floor muscle exercises and behavioral therapy. Properly selected and informed patients can also be treated efficiently with minimally invasive procedures such as the implantation of a male suburethral sling, although the experience with such devices is not extensive. However, the implantation of artificial urinary sphincter is the gold standard therapy.

Despite relative stable and adequately controlled background pain, Breakthrough Cancer Pain (BTcP) is a transient exarcebation of pain that occurs either spontaneously or in relation to a specific predictable trigger. It is characterized by a typical temporal pattern which includes a short onset (generally a few minutes) and a short duration (30-90 minutes). It has a strong influence on quality of life (QoL), including detrimental effects on activities of daily living, sleep, social relationships and enjoyment of life. Therefore, BTcP represents an important clinical challenge in the care of patients with cancer. Transmucosal fentanyl, a rapid onset opioid (ROO), is indicated for the treatment of BTcP in patients who are already receiving and are tolerant to opioid therapy for underlying, persistent pain. In order to identify published studies on BTcP and ROOs a Medline search was carried out. The characteristics of the various formulations of transmucosal fentanyl used for BTcP and clinical data published in literature will be described in this review.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used for acute and chronic pain control and treatment of inflammation, osteoarthritis and rheumatoid arthritis. NSAIDs have been shown to inhibit bone healing in animal studies due to the inhibition of prostaglandin synthesis. However, little evidence exists regarding the effect of NSAID exposure on human bone metabolism. This systematic review summarizes the current literature of randomized controlled trials (RCTs) investigating NSAIDs with bone remodeling-related outcomes in humans. After performing computerized searches in the most widely indexed databases, study selection, data abstraction and risk of bias assessment were conducted in duplicate. The results were controversial regarding the association of NSAID with bone formation or resorption. Increased bone mineral density following NSAID exposure was reported by some studies. Based on the levels of biochemical markers, no effect was seen on bone formation, while some evidence was found for a decreased rate of bone resorption in NSAID patients. Trials investigating the effects of NSAID treatment on bone metabolism outcomes of human patients are limited. Further research is required to confirm or refute the findings of this systematic review.

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is an increasingly used technique by the interventional pulmonologist in lung cancer staging and diagnosis of both malignant and benign mediastinal lymphadenopathy amongst other applications. There are increasing data to support the use of EBUS-TBNA over mediastinoscopy as a first staging or diagnostic procedure in defined situations. In this review, the technique of EBUS-TBNA is briefly discussed with a more extended discussion around comparative studies of mediastinal staging techniques, with an emphasis on the recent ASTER trial as well as impending trials and diagnostic performance studies of EBUS-TBNA in sarcoidosis.