Experimental evidence of a φ Josephson junction.

We demonstrate experimentally the existence of Josephson junctions having a doubly degenerate ground state with an average Josephson phase ψ=±φ. The value of φ can be chosen by design in the interval 0<φ<π. The junctions used in our experiments are fabricated as 0-π Josephson junctions of moderate normalized length with asymmetric 0 and π regions. We show that (a) these φ Josephson junctions have two critical currents, corresponding to the escape of the phase ψ from -φ and +φ states, (b) the phase ψ can be set to a particular state by tuning an external magnetic field, or (c) by using a proper bias current sweep sequence. The experimental observations are in agreement with previous theoretical predictions.

Sex differences in change over time in perceptual asymmetry.

Male (N = 36) and female (N = 43) subjects were given a 120 trial, fused dichotic word test. Males showed higher right ear advantages on the first 60 trials, that then decreased over the next 60 trials. Females showed lower right ear advantages on the first 30 trials, that then increased. The two groups had equal mean asymmetry scores for the last 60 trials. These data suggest that males respond to the novelty of a new task with relative left hemisphere activation while females respond with relative right hemisphere activation. There are no previous reports of sex differences in changes in asymmetry over time.

Ethical dilemmas in pain management.

The purpose of this study was to survey the membership of the American Pain Society and the American Academy of Pain Medicine to determine their beliefs about ethical dilemmas in pain management practice. Respondents rated ethical dilemmas for their importance as well as their own competence in dealing with these ethical issues. The survey also included an open-ended question that asked respondents to describe clinical situations in which they had encountered ethical dilemmas. A total of 1,105 surveys were analyzed, with physicians (N = 612), nurses (N = 189), and psychologists (N = 166) representing the professions with the greatest response. Management of pain at the end of life, general undertreatment of pain, and undertreatment of pain in the elderly were the most frequently encountered dilemmas. Qualitative data were analyzed to identify ethical issues in the case examples provided by the respondents. Major themes included inappropriate pain management, barriers to care, interactions and conflicts with others, regulatory/legal issues, euthanasia, assisted suicide, and research issues. We conclude that ethical dilemmas are common in pain management practice and that resolution of these dilemmas requires commitment by individual professionals as well as health systems.

Psychological and pharmacological therapy: methods and modes for comparative outcome research.

Psychological and pharmacological comparative outcome studies are reviewed, typically using select examples of cognitive-behavioral interventions from among the psychological therapies and of depression from among the disorders. Special attention is given to methodological considerations such as selecting outcome measures, calibrating the quality of therapy, and investigating client and therapist characteristics and the therapeutic relationship. Discussion includes consideration of various modes of comparison (i.e., quickness of action, side effects, relapse, compliance, cost-effectiveness) that may be used in comparative outcome studies. A disorder-specific approach to comparative outcome research is seen as a necessary step in the progress toward an increasingly sophisticated discrimination of distinctive, complementary, and interactive therapeutic processes.

Depression and selection of positive and negative social feedback: motivated preference or cognitive balance?

In this commentary we examine Swann, Wenzlaff, Krull, and Pelham's (1992) findings with respect to each of 5 central propositions in self-verification theory. We conclude that although the data are consistent with self-verification theory, none of the 5 components of the theory have been demonstrated convincingly as yet. Specifically, we argue that depressed subjects' selection of social feedback appears to be balanced or evenhanded rather than biased toward negative feedback and that there is little evidence to indicate that depressives actively seek negative appraisals. Furthermore, we suggest that the studies are silent with respect to the motivational postulates of self-verification theory and that a variety of competing cognitive and motivational models can explain Swann et al.'s findings as well as self-verification theory.

The incremental value of internet-based instruction as an adjunct to classroom instruction: a prospective randomized study.

PURPOSE: Computer-based methods of instruction offer the possibility of helping medical students to learn clinical skills and professionalism. Without rigorous documentation of its pedagogic advantages, the utility of Internet-based teaching is not solidly grounded. The authors carried out a prospective, randomized study of educational outcomes, comparing a traditional classroom course in clinical ethics with the same course supplemented by Internet-based discussion. METHODS: Introduction to Clinical Ethics is a sophomore medical school course that teaches a specific method for analyzing clinical ethical problems. One sophomore class was randomly assigned to either classroom teaching alone (traditional group; n = 65) or classroom teaching supplemented with Internet-based discussions of cases illustrating ethical issues (Internet component group; n = 62). A final case analysis comprehensively evaluated students' understanding of the analytic method taught in the course. Grades for both groups on the final case analyses, which were rated by two external reviewers, were compared. RESULTS: The students' understanding of ethical analysis, as measured by grades of external reviewers on the final paper, was significantly higher for those in the course with the Internet component than it was for those in the traditional course (3.0 +/- 0.6 and 2.6 +/- 0.7, respectively; p <.005). CONCLUSION: The study documents the incremental value of Internet-based teaching of clinical ethics to sophomore medical students.

Damage to liposomal lipids: protection by antioxidants and cholesterol-mediated dehydration.

Liposomes composed of egg phosphatidylcholine (EPC) (13.4%, of the acyl chains being polyunsaturated fatty acids (PUFA)) and EPC/cholesterol (10:1 mol/mol) were studied for factors that affect liposomal lipid oxidative damage and hydrolysis upon long-term (16 months) storage. Factors studied include: (1) levels of lipid/water interface hydration, related to the presence of cholesterol in the lipid bilayer; (2) the membrane-associated antioxidant vitamin E; (3) the water-soluble antioxidant Tempol; and (4) exposure to light. Liposomal dispersions were stored at room temperature, either exposed to or protected from daylight, for a period of 16 months. Chemical and physical changes were monitored at several time points to assess oxidative and hydrolytic degradation of liposomal lipids. The conclusions of the study are: (1) PUFA are the most sensitive component of the liposome bilayer to oxidative degradation damage during long-term storage; (2) EPC liposomes are more sensitive to degradation during storage than EPC cholesterol liposomes, the presence of cholesterol in the lipid bilayer having a protective effect, probably due to its effect in decreasing the lipid-bilayer hydration; (3) oxidative degradation is the major process during long-term storage, having an earlier onset than the hydrolytic degradation: and (4) Tempol provided significantly better protection than vitamin E to EPC liposomal PUFA against oxidative damage during long-term storage. The relevance of cholesterol's presence, as a 'drying agent', in membranes containing PUFA to resistance of biological membranes to oxidative damage is discussed.

Drug therapy for anxiety in palliative care.

BACKGROUND: Anxiety is common among patients with advanced disease. It can be a natural response to impending death, but may also result from an underlying anxiety disorder, pain, or other untreated or poorly managed symptoms. OBJECTIVES: The primary objective of this review was to identify and evaluate studies examining medications used to treat patients suffering from anxiety during the terminal phases of disease. SEARCH STRATEGY: We searched the following sources: MEDLINE (1966 to July 2003), EMBASE (1980 to July 2003), CINAHL (1982 to July 2003), PsycLit (1974 to July 2003), PsycInfo (1990 to July 2003), and the Cochrane Library (Issue 2, 2003) for literature pertaining to this topic published in any language using a detailed search strategy. SELECTION CRITERIA: Prospective, randomized trials with or without blinding involving the use of pharmacological agents for the treatment of anxiety at the end of life were sought. DATA COLLECTION AND ANALYSIS: Six potential studies were identified by the search strategy but none met the criteria for inclusion in this review. Two of these studies assessed the effectiveness of alprazolam in patients with a diagnosis of cancer, but who would not be considered in the end-stage of life. MAIN RESULTS: No data were available to enable an assessment to be made of the effectiveness of drugs to treat anxiety in palliative care patients. REVIEWER'S CONCLUSIONS: There remains insufficient evidence to draw a conclusion about the effectiveness of pharmacotherapy for anxiety in terminally ill patients. To date no studies were found that met the inclusion criteria for this review. Prospective controlled clinical trials are necessary in order to establish the benefits and harms of pharmacotherapy for the treatment of anxiety in palliative care.

Drug therapy for delirium in terminally ill patients.

BACKGROUND: Delirium is a common disorder that often complicates treatment in patients with life-limiting disease. Delirium is described using a variety of terms such as agitation, acute confusional states, encephalopathy, organic mental disorders, and terminal restlessness. Delirium may arise from any number of causes, and treatment should be directed at addressing these causes. In cases where this is not possible, or does not prove successful, the use of drug therapy may become necessary. OBJECTIVES: The primary objective of this review was to identify and evaluate studies examining medications used to treat patients suffering from delirium during the terminal phases of disease. SEARCH STRATEGY: We searched the following sources: MEDLINE (1966 to July 2003), EMBASE 1980 to July 2003), CINAHL (1982 to July 2003), PSYCH LIT (1974 to July 2003), PSYCHINFO (1990 to July 2003) and the Cochrane Library Volume 2, 2003) for literature pertaining to this topic. SELECTION CRITERIA: Prospective trials with or without randomization and/or blinding involving the use of pharmacological agents for the treatment of delirium at the end of life were considered. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality using standardized methods and extracted data for evaluation. Outcomes related to both efficacy and adverse effects were collected. MAIN RESULTS: Thirteen potential studies were identified by the search strategy. Of these, only one study met the criteria for inclusion in this review. This study evaluated 30 hospitalized AIDS patients receiving one of three different agents: chlorpromazine, haloperidol, and lorazepam. Analysis of this trial found chlorpromazine and haloperidol to be equally effective. Chlorpromazine was noted to slightly worsen cognitive function over time but this result was not significant. The lorazepam arm of the study was stopped early as a consequence of excessive sedation. REVIEWERS' CONCLUSIONS: The data from one study of 30 patients would perhaps suggest that haloperidol is the most suitable drug therapy for the treatment of patients with delirium near the end of life. Chlorpromazine may be an acceptable alternative if a small risk of slight cognitive impairment is not a concern. However, there is insufficient evidence to draw any conclusions about the role of pharmacotherapy in terminally ill patients with delirium, and further research is essential.

Analgesic drugs for neuropathic and sympathetically maintained pain.

A variety of pharmacologic approaches to the management of pain due to nerve damage have been tried, with mixed results. Sympathetically maintained pain responds most commonly to sympathetic nerve blocks. Oral nifedipine may be a useful adjunct. Many-but not all-neuropathic pain patients experience relief from low-dose tricyclic antidepressants. When those drugs are not sufficient, the addition of an anticonvulsant, systemic local anesthetic, or both, to the antidepressant may be useful. Neuropathic pain with a major cutaneous component may respond well to topical therapy with the Substance P depletor capsaicin to reduce elevated prostaglandin levels. Topical therapy is most commonly used as an adjunct to systemic drugs. There is now good evidence that early treatment of acute herpes neuralgia with famciclovir may be effective in reducing postherpetic neuralgia. The role of opioids in chronic nerve pain is unclear. Most patients do not respond to these drugs, and should not receive them. Many patients with chronic neuropathic or sympathetically maintained pain need detoxification from opioids, sedative-hypnotics, and muscle relaxants. Some patients cannot carry out normal activities of daily living without opioids, however, and function well while taking low-dose, regularly scheduled opioids. The prognosis for successfully managing neuropathic and sympathetically maintained pain is greatly improved if appropriate therapy is initiated early in the course of the pain. When patients do not respond adequately to initial drug therapy, referral to an interdisciplinary pain management program for evaluation may be in order. Many neuropathic and SMP patients have complex pain syndromes which are most effectively managed through a coordinated, interdisciplinary approach. Careful attention to medical, pharmacologic, psychologic, and physical factors are the hallmarks of this type of treatment. The drugs now available provide marked relief to the majority of patients when therapy includes careful attention to the various dimensions of the pain syndrome. Although consistently effective drug therapy for all neuropathic and sympathetically maintained pain is not yet available, the probability of new NMDA antagonists being introduced in the next few years offers promise.

Esophageal transit of capsules in clinically normal cats.

OBJECTIVE: To evaluate the esophageal passage of capsules in clinically normal cats and determine the incidence of prolonged transit or entrapment. ANIMALS: 12 clinically normal adult cats. PROCEDURE: Esophageal transit of barium sulfate-filled capsules was evaluated fluoroscopically. Each cat was examined 3 times (36 examinations). Esophageal transit times were classified as normal (< or = 30 seconds) or prolonged (> 30 but < or = 240 seconds). Capsules were considered entrapped when transit times were > 240 seconds. RESULTS: Transit times were normal in 10 of the 36 (27.8%) examinations, whereas times were prolonged in 7 (19.4%) examinations. Capsules became entrapped in the midcervical region of the esophagus during 19 (52.8%) examinations. Following termination of each examination, cats with entrapped capsules were fed a small amount (0.5 to 1 ounce) of food; this resulted in passage of the capsule to the stomach. CONCLUSIONS AND CLINICAL RELEVANCE: The possibility of medication-induced esophagitis should be considered when orally administering ulcerogenic drugs to cats. It is recommended that a small volume of food be given following medications to ensure complete esophageal clearance.

Integrating clinical and distributive pharmaceutical services: implications for clinical pharmacy education.

For over two decades, pharmaceutical educators and practitioners have debated whether clinical and distributive pharmaceutical services should be integrated or segregated, i.e., performed by different persons. The recently defined new federal system for reimbursing hospitals for care of Medicaid patients and other beneficiaries according to a prospective reimbursement plan impacts directly on this debate. A cross section of the profession has recently reached consensus on the definition of clinical pharmacy at a national invitational workshop. Fiscal constraints also impacted on the question in schools which are no longer able to keep expanding their clinical faculties. These factors are related questions which academic clinical pharmacy must face are discussed.

Feasibility of international data collection and feedback on post-operative pain data: proof of concept.

Post-operative pain exacts a high toll from patients, families, healthcare professionals and healthcare systems worldwide. PAIN-OUT is a research project funded by the European Union's 7th Framework Program designed to develop effective, evidence-based approaches to improve pain management after surgery, including creating a registry for feedback, benchmarking and decision support. In preparation for PAIN-OUT, we conducted a pilot study to evaluate the feasibility of international data collection with feedback to participating sites. Adult orthopaedic or general surgery patients consented to participate between May and October 2008 at 14 collaborating hospitals in 13 countries. Project staff collected patient-reported outcomes and process data from 688 patients and entered the data into an online database. Project staff in 10 institutions met the enrolment criteria of collecting data from at least 50 patients. The completeness and quality of the data, as assessed by rate of missing data, were acceptable; only 2% of process data and 0.06% of patient-reported outcome data were missing. Participating institutions received access to select items as Web-based feedback comparing their outcomes to those of the other sites, presented anonymously. We achieved proof of concept because staff and patients in all 14 sites cooperated well despite marked differences in cultures, nationalities and languages, and a central database management team was able to provide valuable feedback to all.

Opioid-induced bowel disorders and narcotic bowel syndrome in patients with chronic non-cancer pain.

BACKGROUND: Opioids are used increasingly in the management of moderate-to-severe chronic non-cancer pain (CNCP). Opioid-induced bowel disorders (OBD) markedly impact health-related quality of life (HRQoL) and frequently limit medically indicated opioid pharmacotherapy. We assessed the risk factors, and effect of OBD on HRQoL in CNCP patients. We also estimated the likely prevalence of narcotic bowel syndrome (NBS). These effects have been reported in cancer patients but not in CNCP previously. METHODS: Ambulatory CNCP patients (n = 146) taking regularly scheduled opioids were invited to complete the Bowel-Disease-Questionnaire and a pain-sensitive HRQoL instrument. The Rome-II criteria were used to define bowel disorders. Narcotic bowel syndrome was defined as presence of daily severe to very-severe abdominal pain of more than 3 months duration requiring more than 100 mg of morphine equivalent per day. KEY RESULTS: Ninety-eight patients (69%) returned the survey. Respondents had taken opioids for 10 days to 10 years (median 365 days) at a median daily dose of 127.5 mg morphine-equivalent (range 7.5-600 mg). Constipation prevalence was 46.9% (95% CI 36.8-57.3), nausea 27% (95% CI 17.2-35.3), vomiting 9% (95% CI 17.2-35.3), and gastro-esophageal reflux disease 33% (95% CI 23.5-42.9). Chronic abdominal pain was reported by 58.2% (95% CI 53.2-73.9) and 6.4%, (95% CI 2.4-13.5) fulfilled the criteria of NBS. Prevalence of constipation increased with duration of treatment. Health-related quality of life was low in patients with chronic abdominal pain. CONCLUSION & INFERENCES: Bowel disorders including chronic abdominal pain and NBS are common in patients taking opioids for CNCP. Decreased HRQoL in patients with CNCP is driven by chronic abdominal pain.