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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oral doxepin rinse has been reported to provide pain relief in patients with oral mucosal lesions due to cancer or cancer therapy. The purpose of this study was to assess the anesthetic effect of doxepin oral rinse in normal subjects to identify the duration of effect and to contrast the anesthetic effect with reported pain relief in patients with oral mucosal lesions. Normal volunteers were provided a solution of doxepin (5 mg/mL) for oral rinsing. Oral numbness and adverse effects were recorded for a period of 4 h after rinsing. Doxepin rinse resulted in mucosal anesthesia in all subjects. Sedation/fatigue was reported in four of seven subjects. There were no taste complaints and no nausea reported. The limited duration of numbness/anesthesia in normal subjects compared with prior studies showing pain relief for more than 3 h in patients with mucosal lesions, suggests that the extended duration of pain relief in patients was due to analgesic effects rather than anesthetic effects. The majority of normal subjects reported sedation after use, but this was less common in patients with mucosal lesions.
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PMID:Oral topical doxepin rinse: anesthetic effect in normal subjects. 1467 13

There are many side effects of opioids used for cancer and non-cancer pain, which can limit their use and vastly undermine the quality of life for patients. Sedation is a frequent and serious side effect of opioid analgesics, sometimes reported as fatigue or tiredness from patients. There are a number of specific therapies to control or manage these adverse effects, making it feasible to dose opioids to adequate analgesia with tolerable side effects. The balance between effect and side effects is the goal of chronic opioid pharmacotherapy. In particular, sedation commonly can be problematic in a patient who is taking opioids, to the extent that one may want to discontinue the medication and suffer with the pain rather than experience debilitating fatigue or sedation. When sedation clinically becomes excessive, measures should be taken to make it possible to continue treatment with analgesics with acceptable sedation management. There are many techniques to oppose sedation including simple antidotes, such as rest, exercise, and timing of opioid medications, and more complex solutions, such as opioid rotation and the use of psychostimulants or other classes of medications to counteract sedation. The treatment of opioid-induced sedation can be very effective and should be part of a skill set that the clinician can easily employ to enhance the quality of life of patients.
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PMID:The management of opioid-related sedation. 1600 38

Although palliative sedation therapy is often required in terminally ill cancer patients to achieve acceptable symptom relief, empirical data supporting the ethical validity of this approach are lacking. The primary aim of this study was to systematically investigate whether empirical evidence supports the ethical validity of sedation. This was a multicenter, prospective, observational study, which was conducted by 21 specialized palliative care units in Japan. One-hundred two consecutive adult cancer patients who received continuous deep sedation were enrolled. Continuous deep sedation was defined as the continuous use of sedative medications to relieve intolerable and refractory distress by achieving almost or complete unconsciousness until death. Prior to the study, we conceptualized the ethical validity of sedation from the viewpoints of physicians' intent, proportionality, and autonomy. Sedation was performed mainly with midazolam and phenobarbital. The initial doses of midazolam and phenobarbital were 1.5 mg/hour and 20 mg/hour, respectively. Main administration routes were continuous subcutaneous infusion and continuous intravenous infusion, and no rapid intravenous injection was reported. Of 59 patients who received artificial hydration or could intake adequate fluids/foods orally before sedation, 63% received artificial hydration therapy after sedation, and in the remaining patients, artificial hydration was withheld or withdrawn due to fluid retention symptoms and/or patient wishes. Of 66 patients who were able to verbally express themselves, 95% explicitly stated that symptoms were intolerable. The etiologies of the symptoms requiring sedation were primarily related to the progression of the underlying malignancy, such as cancer cachexia and organ failure, and standard palliative treatments had failed: steroids in 68% of patients with fatigue, opioids in 95% of patients with dyspnea, antisecretion medications in 75% of patients with bronchial secretion, antipsychotic medications in 74% of patients with delirium, and opioids in all patients with pain. On the basis of the Palliative Prognostic Index, 94% of the patients were predicted to die within 3 weeks. Before sedation, 67% of the patients expressed explicit wishes for sedation. In the remaining 34 patients, previous wishes for sedation were noted in 4 patients, and in the other 30 patients, the families were involved in the decision-making process. The chief reason for patient non-involvement in the decision making was cognitive impairment. These data indicate that palliative sedation therapy performed in specialized palliative care units in Japan generally followed the principles of double effect, proportionality, and autonomy.
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PMID:Ethical validity of palliative sedation therapy: a multicenter, prospective, observational study conducted on specialized palliative care units in Japan. 1625 95

To evaluate acute onset of anxiolytic activity using a dental anxiety model, 89 patients were randomised to double-blind single dose pregabalin 150 mg, alprazolam 0.5 mg or placebo 4 h before a scheduled dental procedure. A Dental Anxiety Total score >12 (moderate-to-severe) without meeting Diagnostic and Statistical Manual of Mental Disorders (Fourth edition) (DSM-IV) anxiety disorder criteria was required. Efficacy and safety, assessed 2, 2.5, 3, 3.5 and 4 h postdose, included 100 mm Visual Analogue Scale for Anxiety (VAS-Anxiety; primary outcome), 100 mm VAS-Sedation and Time-to-Onset of Action Scale (TOAS), a patient-rated anti-anxiety drug-benefit scale (no [0] to full benefit [10]). Mixed model analysis found significantly greater VAS-A improvement slopes for pregabalin (t = -2.47; P = 0.014) and alprazolam (t = -2.39; P = 0.018). There was a significant improvement versus placebo in the TOAS from 2 h through endpoint in alprazolam patients and from 3 h onward in pregabalin patients. Pregabalin produced significantly greater increases in VAS-Sedation versus placebo from 2.5 h through 4 h (2 h onward for alprazolam). Notably, there was a higher correlation between TOAS and VAS-Sedation (r = +0.58) than VAS-Anxiety (r = -0.50) on Spearman's analysis. The majority of Adverse Effects (AEs) were mild, and the most frequent for pregabalin, alprazolam, and placebo, respectively, were fatigue (N = 7, 7, 3), dizziness (N = 6, 3, 3), attention disturbance (N = 3, 1, 0), somnolence (N = 3, 0, 0), feeling abnormal (N = 0, 2, 0) and balance disorder (N = 0, 2, 0). These results suggest that onset of clinically meaningful anxiolytic effect after single-dose pregabalin occurs within the first 3-4 h. Additional research is needed to determine whether anxiolytic effect occurs in generalized anxiety disorder populations by day 1 or within 3-4 h post-first dose.
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PMID:Early onset anxiolytic efficacy after a single dose of pregabalin: double-blind, placebo- and active-comparator controlled evaluation using a dental anxiety model. 1863 90


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