Clinical drug investigation
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A non-oncology dose selection phase II trial tests multiple active doses in a controlled fashion, and it not only needs to determine whether the treatment is effective but also to select the 'lowest efficacious' dose if the treatment is indeed efficacious. Few approaches exist in the literature for designing phase II non-oncology dose selection trials, and the standard design with a fixed sample size has been widely used. The objective of this study was to develop a more efficient design for phase II dose selection trials that terminates the trial early for futility and adjusts the sample size and number of doses at interim analyses when appropriate. ⋯ Once a confident answer to either or both of these questions can be obtained, the trial may either be terminated early or some of the lower doses may be dropped to prevent assigning more patients to inferior doses and thus reduce the total sample size needed. Theoretical analyses and simulation studies show that the proposed adaptive design significantly outperforms the standard design with a fixed sample size. The proposed adaptive design should be preferred over the standard design especially in cases where enrolment is slow and efficacy can be measured after a relatively short period of time.
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Multicenter Study
Prevalence and characterization of neuropathic pain in a primary-care setting in Spain: a cross-sectional, multicentre, observational study.
Different studies have shown pain to be one of the most frequent causes of health-care resource utilization, and a major public health concern because of its social repercussions. In Spain there are no recent data on the prevalence and management of neuropathic pain in the general primary-care setting. ⋯ The results of the present study show the high prevalence of neuropathic pain at the primary-care level in Spain. In addition, the data presented here point to a need to improve the management of outpatients with neuropathic pain in the Spanish primary-care setting, particularly in relation to the higher than recommended use of NSAIDs (which are not indicated for neuropathic pain) and the lower than recommended use of antiepileptic drugs with an analgesic indication for pain with a neuropathic component.
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Review
Pain treatment with opioids : achieving the minimal effective and the minimal interacting dose.
Appropriate and successful management of pain with opioid analgesics is based on tailoring pharmacologic treatment to the individual and identifying the minimal effective dose at which pain is controlled with minimal adverse effects. Morphine and morphine-like-agonists exhibit similar pharmacodynamic profiles, but substantially different receptor affinities and pharmacokinetic properties, which dictate the dosage, route and regimen required to achieve analgesic effect. Opioids exhibit differences in drug elimination resulting in marked variations in the plasma half-life value. ⋯ Dose titration is the key to successful therapy initiation with strong opioids in patients with moderate-to-severe pain. It is the only way to establish the optimal and minimal effective dose and provides the best protection against adverse effects. Committed physicians should adhere to guidelines on the appropriate use of opioids in all patients, particularly those with a high risk of adverse reactions.
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Multicenter Study Clinical Trial
Adequacy assessment of oxycodone/paracetamol (acetaminophen) in multimodal chronic pain : a prospective observational study.
Multimodal pain is comprised of nociceptive/inflammatory and neuropathic components. Pharmacological pain therapies from different classes provide pain relief using different mechanistic actions; often a combination of such therapies provides more effective pain relief than monotherapy. To assess whether pain management is adequate requires a comprehensive pain scoring system. ⋯ The PMI was an effective tool for assessment of pain management efficacy. Oxycodone/paracetamol improved pain symptoms in the majority of compliant patients. In patients with neuropathic pain, rescue therapy with oxycodone/paracetamol showed a lesser, but significant, improvement of pain symptoms.
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Monotherapy with any class of antihypertensive drug effectively controls blood pressure (BP) in only about 50% of patients. Consequently, the majority of patients with hypertension require combined therapy with two or more medications. This study aimed to evaluate the effectiveness (systolic BP [SBP]/diastolic BP [DBP] control) and tolerability of the fixed-dose combination enalapril/nitrendipine 10 mg/20 mg administered as a single daily dose in hypertensive patients. ⋯ The rate of SBP/DBP control achieved demonstrates the effectiveness of the fixed-dose enalapril/nitrendipine 10 mg/20 mg combination administered as a single daily dose in patients with essential hypertension not adequately controlled with monotherapy or with any combination other than enalapril + nitrendipine. The proportion and type of adverse events reported were as expected and have already been described for both components of the enalapril/nitrendipine 10 mg/20 mg combination. These results confirm the effectiveness of a strategy based on a fixed-dose enalapril/nitrendipine 10 mg/20 mg combination in reducing BP and achieving BP control goals.