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.

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.

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.

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.

Treatment of chronic pain in osteoarthritis: do opioids have a clinical role?

Pain is the most prominent symptom and clinical finding in osteoarthritis (OA). Acetaminophen and nonsteroidal anti-inflammatory drug (NSAID) therapy are the mainstays of OA analgesia, but other drug and non-drug therapy, joint injections, and surgery may be needed to provide reasonable quality of life. Regularly scheduled, low-dose opioids can produce good relief of chronic nonmalignant pain including pain caused by OA. This paper reviews the potential risks and benefits of opioids, the evidence supporting their use in OA pain, and guidelines for their use in OA pain.

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.

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.

Ketorolac in the era of cyclo-oxygenase-2 selective nonsteroidal anti-inflammatory drugs: a systematic review of efficacy, side effects, and regulatory issues.

OBJECTIVE: The recent introduction of oral COX-2 selective NSAIDs with potential for perioperative use, and the ongoing development of intravenous formulations, stimulated a systemic review of efficacy, side effects, and regulatory issues related to ketorolac for management of postoperative analgesia. DESIGN: To examine the opioid dose sparing effect of ketorolac, we compiled published, randomized controlled trials of ketorolac versus placebo, with opioids given for breakthrough pain, published in English-language journals from 1986-2001. Odds ratios were computed to assess whether the use of ketorolac reduced the incidence of opioid side effects or improved the quality of analgesia. RESULTS: Depending on the type of surgery, ketorolac reduced opioid dose by a mean of 36% (range 0% to 73%). Seventy percent of patients in control groups experienced moderate-severe pain 1 hour postoperatively, while 36% of the control patients had moderate to severe pain 24 hours postoperatively. Analgesia was improved in patients receiving ketorolac in combination with opioids. However, we did not find a concomitant reduction in opioid side effects (e.g., nausea, vomiting). This may be due to studies having inadequate (to small) sample sizes to detect differences in the incidence of opioid related side effects. The risk for adverse events with ketorolac increases with high doses, with prolonged therapy (>5 days), or invulnerable patients (e.g. the elderly). The incidence of serious adverse events has declined since dosage guidelines were revised. CONCLUSIONS: Ketorolac should be administered at the lowest dose necessary. Analgesics that provide effective analgesia with minimal adverse effects are needed.

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.

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.

Effects of acetabular abduction on cup wear rates in total hip arthroplasty.

This study was designed to determine the effect of acetabular abduction on the polyethylene wear rates of the acetabular component. The hypothesis of this study is that acetabular placement, in particular abduction, effects contact forces and therefore polyethylene wear. A total of 364 total hip arthroplasties that were performed between 1974 and 1976 were included in this study. The cemented all-polyethylene acetabular components were the same for each case and came from a single supplier. The polyethylene wear rates were calculated by measuring the shortest radius from the center of the prosthetic femoral head to a point on the outer surface of the acetabular cup. An immediate postoperative radiograph was compared with a follow-up radiograph at least 9.5 years later. A standardized radiograph was used to prevent differences due to magnification. The abduction or inclination of the acetabular cups was measured in all of the patients. The amount of acetabular cup abduction was measured relative to the ischial tuberosity line. The mean abduction was 44.1 degrees with a standard deviation of 9.2 degrees and a median of 44 degrees. The range of abduction was from 0 degrees to 85 degrees. This analysis failed to show a correlation between the amount of acetabular abduction and polyethylene wear rates (Pearson's correlation coefficient = 0.0679; P = .20). With a sample size of 364, there is over a 95% change (statistical power) of detecting an underlying true correlation between wear and abduction that is greater than or equal to 0.20. We were unable to demonstrate a difference in wear that would correlate with the differing degrees of abduction of the acetabular socket. We felt that the radiographic measurements of wear were quite accurate. This method of determining acetabular abduction has also been documented and supported in previous literature and has allowed us to accurately determine acetabular abduction. The results of our study demonstrate that within the normal ranges described by our study, polyethylene wear did not significantly increase with increased abduction of the acetabular component.

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.

Management of pain in the cancer patient.

The pain experience of the cancer patient is the result of many factors, including nociceptive sources, specific pain syndromes, and behavioral contributions. Careful evaluation of the patient is necessary to identify the contributors to the patient's pain experience and to select treatment modalities which address the underlying causes. For patients who are experiencing poorly controlled pain as a result of cancer, therapy often includes multiple management strategies involving more than one discipline. Therefore, an interdisciplinary approach may be more useful for pain management. Disciplines and specialties. involved in such care commonly include anesthesiologists, oncologists, psychiatrists, psychologists, physical therapists, pharmacists, nurses, and social workers. The locus of control often influences how patients respond to their physicians' advice. Patients with a strong internal locus of control usually want to participate actively in treatment decisions. Such patients often resent having decisions made about their treatment without their participation. A lack of sense of control can exacerbate such patients' pain and limit compliance with recommended treatments. Drug therapy is the mainstay of cancer pain management. The therapy should be individualized to the patient, and medications should be selected for specific indications. The WHO three-step analgesic ladder should be used as a guide in selecting analgesics. Drugs should be administered by mouth unless it is impossible to do so, and drug costs should be considered when selecting analgesic medications. Doses should be titrated to response. Adjuvant drug therapy should be considered early and implemented when indicated. Practitioners should be familiar with the medications prescribed and be alert for the appearance of adverse side effects. Patients should be monitored and reassessed continuously. A thorough diagnostic work-up should be completed for new symptoms when indicated. For patients with specific pain syndromes, or for whom drug therapy has not been successful, local anesthetic and neurolytic block therapy and more invasive drug delivery systems (e.g., epidural catheters) should be considered. Although cure may not be attainable in many cancer patients, the obligations of health professionals to these patients are no less than to patients for whom a cure is achievable. Effective pain management has a profound impact on the quality of life, and may give the patient the opportunity to face death with dignity and reduced suffering.

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.

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.

Clinically relevant differences among the opioid analgesics.

The mechanism of action of opioids and clinically relevant differences among the opioid analgesics are described. Both endorphins (endogenous morphine-like substances) and exogenous opioids (opium alkaloids and their derivatives) bind to opioid receptors in the human central nervous system to provide analgesia and other effects. Some drugs, such as morphine, are true agonists, i.e., they bind to and activate receptors. Some are partial agonists, binding to part of the receptor and causing effects that are similar to, but perhaps less pronounced than, the effects produced by agonists. Others are antagonist, i.e., they bind to the receptor but do not cause the associated effects. Some drugs, termed agonist-antagonist opioids, act as antagonists at one type of receptor and agonists at another type of receptor. True agonists tend to have relatively straight-line dose-response curves; in other words, their effect increases with increasing doses over a broad dosage range. Partial agonists and agonist-antagonists tend to have ceiling effects; that is, they do not have the broad dosage range of drugs such as morphine, methadone, hydromorphone, and other "strong" opioids. This fact mediates against the use of partial agonists and agonist-antagonists in cancer patients who have chronic pain that may increase as the disease progresses. Three major factors that should be considered when a drug is selected for clinical use are (1) relative affinities for the different opioid receptor types, (2) pharmacokinetic characteristics that influence onset and duration of action, and (3) whether the opioids are strong or weak. For treatment of cancer pain, drugs with long durations of action are preferable.(ABSTRACT TRUNCATED AT 250 WORDS)