Tumor necrosis factor (TNF)-alpha inhibitors are the most common type of biologics used for treating patients with rheumatoid arthritis (RA) who do not respond to methotrexate (MTX) or other disease-modifying antirheumatic drugs (DMARDs). TNF-alpha inhibitors include infliximab, certolizumab pegol, etanercept, golimumab, and adalimumab. 1 Adalimumab is approved globally for treating RA, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, plaque psoriasis, hidradenitis suppurativa, and uveitis. 2
An open-label, randomized, crossover study was performed in healthy male volunteers to evaluate the potential pharmacokinetic and pharmacodynamic interactions and tolerability of single oral doses of modafinil (200 mg) and dextroamphetamine (10 mg). Blood samples were collected for determination of plasma levels of modafinil, the acid and sulfone metabolites of modafinil, and dextroamphetamine at intervals through 48 hours after administration for each treatment. Vital signs (blood pressure and pulse rate) were measured through 48 hours, and electrocardiograms were measured through 24 hours after administration. Pharmacokinetic parameters were determined using noncompartmental methods. The data collected in this study of 24 healthy volunteers suggest that concomitant administration of single oral doses of modafinil and dextroamphetamine has no clinically significant effects on the pharmacokinetic profile of either agent. Although there was a slightly greater incidence of adverse events when modafinil and dextroamphetamine were administered together, the concomitant administration of the two drugs was well tolerated.
Thoracotomy causes severe postoperative pain, which is difficult to manage since the use of systemic analgesics often causes respiratory depression. Cryoanalgesia of the intercostal nerves has been advocated as an effective means of local analgesia without serious side effects. A prospective randomised blind trial to investigate the efficacy of the technique was carried out. A total of 53 patients undergoing thoracotomy were allocated to either the trial or a control group. At thoracotomy the surgeon was informed of the patient's trial allocation. The trial group received one minute of direct cryotherapy to at least five intercostal nerves related to the incision. All patients received methadone via the lumbar epidural route in a dose calculated according to their weight. A linear analogue assessment of postoperative pain was made by the patients as soon as they were sufficiently awake. An independent record of all postoperative analgesia was kept. After discharge from hospital further assessments were made at least six weeks after operation. Statistical analysis of the scores of postoperative pain and analgesic consumption showed that there was no significant difference between the trial and the control group. There was, however, a suggestion of an increase in the long term morbidity, although these figures were not amenable to statistical analysis. Thus it has not been possible to demonstrate a role for cryoanalgesia in the control of post thoracotomy pain.The control of postoperative pain is particularly important in thoracic surgery. Adequate postoperative analgesia must be provided without impairing the remaining respiratory function. There has therefore been some recent interest in local methods of pain relief. It has been shown by this unit that the use of epidural methadone is an effective and safe way of providing analgesia during the early postoperative phase.' It cannot, however, be used for a prolonged period and therefore interest has been focused on cryoanalgesia, which has been said to provide pain relief for up to 26 days.2 Although there are favourable reports of its efficacy,34 the impression in this unit was that there was no subjective benefit. A prospective randomised trial was therefore devised to investigate the effect of adding cryoanalgesia to a standard postoperative analgesic regimen.
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