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Across the 3 treatment groups, with 2 exceptions. A history of previous suicide attempt was more frequent in the lithium group 41% ; compared with the placebo group 19% ; P .01 ; . Among patients who had previously received at least 1 psychotropic medication, fewer patients had previously been treated with valproate in the lithium group 23% ; compared with the placebo group 51% ; P .005 ; or the lamotrigine group 49% ; P .01 ; . In addition to lamotrigine, other psychiatric medications were allowed during the initial part of the openlabel phase and were used by 78% of all patients and 75% of those eventually randomized. Medications used by 10% or more of all patients were lithium 18% ; , lorazepam 18% ; , clonazepam 15% ; , valproate 14% ; , and haloperidol 14% ; . These percentages were only slightly lower for patients who were eventually randomized, except for clonazepam 9% ; and haloperidol 9% ; , and were comparably distributed among the double-blind treatment groups. Of 349 patients who entered the initial open-label phase of the study, 175 50% ; achieved stabilization criteria and entered the double-blind phase of the study. TIME TO ANY MOOD EPISODE Both lamotrigine and lithium were significantly superior to placebo on time to intervention for any mood episode lamotrigine vs placebo, P .02; lithium vs placebo, P .003 ; Figure 1A ; . Lamotrigine and lithium did not differ from each other on this parameter P .46 ; . Median survival times are provided in Table 3. Medications added at the point of intervention included antidepressants n 19 patients ; , lamotrigine n 19 ; , typical antipsychotics n 16 ; , ben REPRINTED ; ARCH GEN PSYCHIATRY VOL 60, APR 2003 396.
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Older adults have increased vulnerability to the side effects and toxicity of anticholinergic drugs because of physiologic and pathophysiologic changes that often occur in the aging process.49 Therefore, cognitive deficits and or nonresponse to dementia treatment may result. With increasing age, drugs are metabolized and eliminated at a slower rate. There are possible changes in the bloodbrain barrier as age-related vascular changes take place. Moreover, there is a decrease in the number and distribution of muscarinic receptors with aging and agerelated deficits in ACh neurotransmission.51 Of importance, as patients age, they are more likely to be prescribed multiple medications with anticholinergic effects, resulting in cumulative anticholinergic burden. Among older adults, there are individual differences in sensitivity to certain anticholinergic-related adverse effects, placing some patients at greater risk of developing anticholinergic side effects.48, 49, 52 In addition to drugs for incontinence, many older adults take medications with anticholinergic effects to treat cardiac conditions, allergic rhinitis, and depression. In many cases, accumulation of different drugs taken by a patient gives rise to anticholinergic toxicity because of additive total anticholinergic activity.53 More than 600 medications from several different pharmacologic classes are known to have anticholinergic activity, and a disproportionately large number of them are frequently prescribed to elderly patients and
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PATIENTS ASSESSMENT OF THE PERIOPERATIVE PERIOD: GENERATING A PILOT QUESTIONNAIRE AND PSYCHOMETRIC TESTING AUTHORS: P. Kranke1, I. Celik2, N. Roewer1, M. Simon3, W. Buendgen1, L. Eberhart3; AFFILIATION: 1Department of Anesthesiology, University of Wuerzburg, Wuerzburg, Germany, 2Department of Surgery, University of Marburg, Marburg, Germany, 3Department of Anesthesiology, University of Marburg, Marburg, Germany. INTRODUCTION: Various methods have been used to quantify patient satisfaction with perioperative care. Most are narrowly focused due to the neglect of patients attitudes and concerns during the development or due to the fact that the core process of the perioperative pathway was subdivided into various aspects i.e. physicians vs. caring professions, anesthesia vs. surgery, "hotel service" vs. medical service. In a previous step of comprehensive and weighted patients vs. relatives vs. healthcare professionals ; item generation we identified 41 key issues that should be further evaluated and processed in a pilot questionnaire using psychometric methods. The aim was to generate a validated and consistent questionnaire to evaluate patients assessment of the perioperative period approximately 1 day prior to surgery until the first or second postoperative day ; . METHODS: Relevant outcomes and circumstances were presented to inpatients as statements in an iterative approach at various institutions university hospitals, private surgery centers ; in Marburg and Wuerzburg, Germany. Patients were asked to rate the given statements on a 4-point likert-scale ranging from "1" at no time not at all true ; to "4" all of the time wholly true ; . RESULTS: In a first step, the 41 most relevant issues of the item generation phase were presented to 157 patients. The obtained ratings were subjected to qualitative and quantitative reliability analysis. Items were eliminated due to lacking responses of more than 10% of the cohort or because a statement was not an issue for more than 90% of patients resulting in impaired discriminating properties. Items with inter-item correlation below 0.2 were eliminated. Based on 114 eligible assessments out of 157 patients the calculation of Crohnbachs alpha was 0.82 for the revised questionnaire with the remaining 33 items. In a second step these 33 items were regrouped and again presented to subsequent patients in the aforementioned institutions. Reliability testing confirmed good positive inter-item correlation. Crohnbachs alpha was calculated to be 0.78. Compliance with this final tool was excellent. Randomized distribution of the questionnaire using other layout or other order chronological order of the statements according to the perioperative path of the patient vs. random order vs. grouping due to main categories ; was irrelevant for the results in both steps. CONCLUSION: Qualitative and quantitative psychometric testing confirms the reliability of the developed questionnaire. Anesthesiarelated issues play a relevant role in the final set of items. Factors that determine results of the patients assessment of the perioperative period, robustness across different patient populations, correlation with other tools visual analog scale, willingness to pay ; or sub-categories of perioperative course i.e.: recovery ; have yet to be determined in subsequent investigations, for instance, clonazepam sleep.
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Dose and after 2 weeks of twice daily administrations, whereas the action of diazepam was clearly decreased after repeated doses. Similarly the partial protection against bicuculline in rats no effect on the incidence of clonic convulsions but reduction of severity ; was maintained after 13 days of treatment. The feasibility of chronic treatment was also evaluated in kindling models see next section ; . Antiepileptogenic activity In rats, levetiracetam exhibited antiepileptic activity both in the amygdala and PTZ kindling models. Daily amygdala stimulation led to seizures of progressively increasing severity score and duration. Chronic treatment with levetiracetam 54 mg kg day i.p. ; delayed the increase in severity, but following discontinuation of the drug the severity finally reached the same level in animals treated or untreated during the kindling process. Measurement of seizure duration or of after-discharge duration led to more conclusive results. The duration remained shorter in levetiracetam-treated animals even 2 weeks after drug discontinuation. From the literature it seems that this effect of levetiracetam is rather unique. Valproate and phenobarbital delayed the increase in severity and duration during kindling, but both parameters rapidly reached control values after treatment termination. General and safety pharmacology programme Central nervous system In mice, levetiracetam produced dose-dependent decreases in spontaneous activity and muscular tone. In rats, performance in the rotarod test was not decreased at doses up to 1700 mg kg, whereas chimney climbing was impaired in the 540-1700 mg kg range. In rats the pentobarbital induced sleeping time was not affected by levetiracetam up to 1800 mg kg orally. The doses required for protection of seizures ED50 ; were compared with the doses inducing rotarod performance impairment TD50 ; in corneally kindled mice. The safety margins TD50 ED50 ratio ; for various antiepileptic agents were as follows: Levetiracetam 148, phenytoin 17, gabapentin 16, vigabatrin 7, lamotrigine 7, carbamazepine 6, clonazepam 3, valproate 3 and phenobarbital 2. In a related study in rats, the TD50 characterising the impairment of rotarod performance were similar and comparable in kindled and non-kindled animals. Levetiracetam had no detectable analgesic action. At 300 mg kg p.o. it slightly decreased the body temperature of rats. No sign of physical dependence was detectable in rats after stopping repeated administrations of levetiracetam after 40 days at doses up to 1800 mg kg day. Cardiovascular system In anaesthetised dogs, an i.v. bolus of levetiracetam, above a threshold dose of 100 mg kg, produced a rapid and transient decrease in blood pressure and aortic blood flow as well as an increase in heart rate. Tachycardia and atrioventricular block were observed at doses above 1 g kg and lethality occurred at 3.2 g kg. In conscious dogs, levetiracetam induced short-lasting increases in heart rate and diastolic blood pressure. An increase in pulmonary artery pressure was observed after i.v. injection of 50-450 mg kg doses. Gastrointestinal system Levetiracetam had no effect on the guinea pig ileum contraction induced by electrical stimulation or by various mediators. Levetiracetam had no effect on gastric secretion in rats, nor on intestinal motility in mice. Immune function Levetiracetam 50-1800 mg kg day p.o. ; did not have any effects on immune function in a 4-week study in rats. No evidence of sensitisation was obtained in various tests in guinea pigs systemic anaphylaxis, passive cutaneous anaphylaxis ; . Pharmacokinetics Absorption of oral levetiracetam was rapid Tmax 1 hour ; and complete. The absolute bioavailability was close to 100% in all species investigated. Tissue distribution was rapid. After 1 hour, the concentrations in most organs were close to the blood concentrations. After 24 hours, the residual organ concentrations were in general higher than the blood level, especially in the brain.
Testicular volumes at the end of the 12 days of FSH or vehicle infusion were statistically indistinguishable Fig. 1 ; . Correspondingly, the mean weights of the right testes collected at the end of FSH stimulation or vehicle administration were the same Table 3 ; . Similarly, the mean weights of the left testes collected 22 days later were statistically indistinguishable Table 3 ; . FSH treatment did not influence either the diameter of seminiferous tubules or the volume fractions of the interstitial and tubular compartments Table 3 ; . Sertoli cells and all types of germ cells from stem spermatogonia to step 14 spermatids were present in testes from both FSH- and and diazepam.
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The prognosis of papillary thyroid cancer is better than follicular thyroid cancer; however, if the confounding effects of age and extent of tumour at diagnosis are removed, survival rates are comparable.3, 7, 1416 Within the papillary thyroid cancer group, poorer prognosis is associated with specific histological types1720 and the degree of cellular differentiation and vascular invasion.5, 21 `Wide' and `vascular' invasion are features of follicular cancers associated with poor prognosis.19, 22 Poorly differentiated follicular cancers insular carcinoma ; and Hrthle cell carcinomas are also associated with a poor outcome.7, 8, 23.
In children, the benzodiazepines have been used primarily for pain due to muscle and bladder spasm. Although it is not thought that the benzodiazepines have intrinsic analgesic properties, they are potent anxiolytics and anticonvulsants. It may be their anticonvulsant properties that facilitate their use in the treatment of neuropathic pain. Alprazolam, for example, has been shown to be a helpful adjuvant analgesic in the treatment of adults with phantom limb pain Fernandez, Adams & Holmes, 1987 ; . Colnazepam may also be useful in the management of lancinating neuropathic pain and has been reported to be useful for patients with trigeminal neuralgia, headache, and post-traumatic neuralgia Breitbart, Passik & Payne, 1997 ; . The benzodiazepines are also amnesic agents. Cannabinoids Although controversial, and definitive studies are awaited, there are data suggesting the cannabinoids have analgesic and anti-emetic properties Williamson & Evans, 2000 ; . In one paediatric study, delta-8-tetrahydrocannabinol delta-8-THC ; , a cannabinoid with lower psychotropic potency than the main cannabis constituent, was administered to eight children with cancer, aged 3-13 years. Although a small study, the outcomes in terms of emesis and side-effect profile were positive Abrahamov, Abrahamov & Mechoulam, 1995.
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