Improvement of medical judgments by numerical training in patients with multiple sclerosis.

BACKGROUND AND PURPOSE: People with multiple sclerosis (MS) have to face important decisions with regard to their medical treatment. The aim of this study was to evaluate whether a targeted cognitive training reduces framing effects and thus improves medical judgments. METHODS: This was a randomized, double-blind, cross-over study enrolling patients with relapsing-remitting MS and healthy controls (HCs). Participants were randomly assigned to training order A (first week, numerical training; second week, control training) or B (reverse order). The primary endpoint was changed in a framing task score (framing effect). In the framing task, participants evaluated the success of fictive medications on a 7-point scale. Medications were described in either positive or negative terms. RESULTS: A total of 37 patients and 73 HCs performed either training order A (n = 56) or B (n = 54). The framing effect decreased after the numerical training regardless of training order. No such decrease was found after the control training. Mean change in framing effect was -0.3 ± 0.8 after the numerical training and 0.03 ± 0.6 after the control training. This specific effect of training type was comparable between groups. CONCLUSION: Judgments of medical information improve in both patients with relapsing-remitting MS and HCs after a targeted numerical training. Thus, a specific cognitive intervention may help patients making informed decisions.

[Advice for patients diagnosed with ankylosing spondylitis: results of a representative patient survey in Germany]. / Hinweise für Patienten mit der Diagnose Ankylosierende Spondylitis: Ergebnisse einer Repräsentativbefragung der Deutschen Vereinigung Morbus Bechterew e.V.

BACKGROUND: Following the diagnosis of a chronic disease like ankylosing spondylitis (AS), patients need extensive information on what to expect, how to behave and what they need to be aware of in particular in order to contribute to a favourable disease outcome. METHODS: A questionnaire consisting of 82 questions regarding demographics, diagnosis, information received with the diagnosis, disease activity, function, quality of life, treatment, ability to work, smoking etc. was distributed to AS patients by rheumatologists in 51 hospitals and/or private practices. In addition, the questionnaire was sent to 3400 randomly selected members out of the 14,000 patient members of the German Ankylosing Spondylitis Society (Deutsche Vereinigung Morbus Bechterew, DVMB). RESULTS: In all, 1068 DVMB members and 205 non-members responded to the survey. Almost all of these indicated that they had received at least one piece of information regarding what they should be particularly aware of, at the time of diagnosis. A total of 69% were informed about the need for daily exercise, 51% about the value of individual physiotherapy, 38% about the value of group physiotherapy, 37% about the need to maintain an upright posture, and 33% were recommended 3 weeks in a rehabilitation centre. Less than 30% were informed about appropriate sports, appropriate working conditions, suitable chairs, mattress, pillows etc., about the value of radon therapy or about joining a disease-specific patient organisation. To the question regarding what patients meanwhile consider as most important, daily exercise (50%) and sufficient movement at work and leisure (55%) were reported most frequently. Other aspects regarded as important to patients included a flat, firm mattress (53%), avoiding large pillows (42%), keeping an upright posture at work (38%), appropriate sports (36%), and an upright posture also when not at work (34%). Of the DVMB members, 46% had participated in disease-specific standardised patient education, compared with only 31% of non-members (p<0.001).

Colony housing promotes structural and functional changes during surgically induced osteoarthritis in rats.

Objective: The aim of the study was to investigate how social housing with high locomotion activity affects experimental osteoarthritis (OA) in rats. Design: Rats were housed either conventionally in type IV cages in pairs or in rat colony cages (RCC) on 4 levels interconnected by jump holes or staircase in groups of 48. OA was induced by anterior cruciate ligament transection and resection of the medial meniscus (ACLT + tMx), medial meniscal tear (MMT) or destabilization of the medial meniscus (DMM). Functional changes were characterized by continues tracking of individual activity and catwalk gait analysis. Cartilage volume and bone structure were investigated at week 20 after surgery by histology and micro-CT. Results: In the RCC, healthy rats changed cage levels 82 ± 15 times daily, reduced by 30% after ACLT + tMx (p < 0.0001). In both housing systems, the order of severity of the investigated models was ACLT + tMx > MMT > DMM in all outcome measures. Compared to Type IV, RCC housed rats developed stronger gait disturbance symptoms (ACLT + tMx; 95%CI = -15-2; p < 0.004), the cartilage volume was reduced (ACLT + tMx: 95%CI = -0.1-0.5; p < 0.0001), serum levels of the cartilage remodeling marker AGNx1 were higher (MMT; 95%CI = -53-(-6); p = 0.001), bone was denser with increased volume (ACLT + tMx; 95%CI = 0.8-7.5; p = 0.004) and joints were less flexible (ACLT + tMx; 95%CI = 3.6-14; p < 0.0001). Conclusion: Housing rats in an environment allowing increased locomotion and socialization promotes structural and functional alterations during joint instability-induced OA. This increases the assay window, improves the relevance for the human disease and enables to discriminate the models in structural and behavioral parameters.

Inhibition of cyclooxygenases by dipyrone.

BACKGROUND AND PURPOSE: Dipyrone is a potent analgesic drug that has been demonstrated to inhibit cyclooxygenase (COX). In contrast to classical COX-inhibitors, such as aspirin-like drugs, dipyrone has no anti-inflammatory effect and a low gastrointestinal toxicity, indicating a different mode of action. Here, we aimed to investigate the effects of dipyrone on COX. EXPERIMENTAL APPROACH: The four major metabolites of dipyrone, including the two pharmacologically active metabolites, 4-methyl-amino-antipyrine (MAA) and amino-antipyrine (AA), were used to characterise their binding to COX and haem as well as their effects on the biochemical properties of COX. Mass spectrometry, UV and visible photometry were used to study binding and prostaglandin production. Levels of anti-oxidant enzymes were assessed by Western blotting. KEY RESULTS: The pharmacologically active metabolites of dipyrone, MAA and AA, did not inhibit COX activity in vitro like classical COX inhibitors, but instead redirected the prostaglandin synthesis, ruling out inhibition of COX through binding to its active site. We found that MAA and AA formed stable complexes with haem and reacted with hydrogen peroxide in presence of haem, ferrous ions (Fe(2+)) or COX. Moreover, MAA reduced Fe(3+) to Fe(2+) and accordingly increased lipid peroxidation and the expression of anti-oxidant enzymes in cultured cells and in vivo. CONCLUSIONS AND IMPLICATIONS: Our data suggest that the pharmacologically active metabolites of dipyrone inhibit COX activity by sequestering radicals which initiate the catalytic activity of this enzyme or through the reduction of the oxidative states of the COX protein.

rFVIIa--for acute rebleeding of a cerebral cavernous malformation.

Recurrent bleeding episodes of cavernomas especially in the brainstem can cause progressive neurological deficits. Therefore brainstem cavernomas are still a therapeutic dilemma and a treatment challenge for the neuro critical care community. We report a 39-year-old woman with spontaneous ataxia diplopia and vomiting, who has been treated for multiple intracerebral cavernomas during the last 10 years. A cerebral computed tomography (cCT) revealed a re-bleeding cavernoma in the left cerebral peduncle with consecutive obstructive hydrocephalus. As a result of the difficult anatomical location, no surgical approach was possible. As an off-label treatment, recombinant activated factor VII (rFVIIa) was administered to prevent possible further bleeding and especially further sequelae. The patient recovered well and no adverse events and especially no further bleeding of the cavernoma were observed. To our knowledge, this is the first report of the safe and successful use of rFVIIa to treat re-bleeding episodes in cavernomas. Further clinical studies are needed to specify the future potential of rFVIIa.

Cortical motor activation patterns following hand transplantation and replantation.

We studied cortical activation patterns by functional MRI in a patient who received bilateral hand transplantation after amputation 6 years ago. In the early post-operative period, the patient who had had the hand transplantation revealed strong activation of a higher motor area, only weak activation of the primary sensorimotor motor cortex and no activation of the primary somatosensory cortex. At one-year follow-up, a small increase in primary sensorimotor motor cortex activation was observed. Activation of the primary somatosensory cortex was only seen at the 2-year follow-up. Transplantation after long-standing amputation results in cortical reorganisation occurring over a two-year period.

Muscle electrophysiology in patients with advanced breast cancer.

Sixty-one consecutive patients with advanced breast cancer (defined as metastatic disease) and 20 normal age- and sex-matched controls were admitted to a prospective study designed to assess muscle electrophysiology. Nutritional status, lean body mass, and ultrasonographic measurement of the triceps brachialis, sternomastoid, and adductor pollicis muscles were determined in patients and controls. In addition, tumor mass and performance status were determined in the patient group. Electrophysiology of the adductor pollicis muscle was assessed during isometric voluntary maximum effort and during electrical stimulation via the ulnar nerve (80-120 V, 50-100 msec). Nutritional status, lean body mass, and ultrasonographic measurements of the triceps brachialis, sternomastoid, and adductor pollicis were not significantly different between patients and controls. Maximum strength after supramaximal stimulation at 50 Hz was 34 +/- 15 N in patients, versus 40 +/- 9 (P less than .01) N in controls. Relaxation velocity was 336 +/- 149 N/sec in patients, versus 507 +/- 251 (P = .02) N/sec in controls. Fatigue (% of initial strength after 30 sec of stimulation) was 67% +/- 22% in patients, versus 79% +/- 17% (P = .03) in controls. Muscle electrophysiology did not correlate with tumor mass or performance status. It was concluded that patients with advanced breast cancer have abnormal muscle electrophysiology that is not due to abnormal nutritional status or decreased muscle mass. More research is needed to better characterize this disorder and to better define its cause.

Patient-controlled subcutaneous hydromorphone versus continuous subcutaneous infusion for the treatment of cancer pain.

Twenty-five patients with pain due to advanced cancer were randomized to receive patient-controlled sc injections (PCIs) of hydromorphone (HM) versus continuous sc infusion (CSCI) of HM by means of a Pharmacia 5200 pump. Each self-injection of HM during PCI was equivalent to 4 hours of CSCI. After 3 days, a crossover occurred, and patients received the alternate treatment for 3 days. During both phases of the study, patients could request extra doses of HM from their nurses. In 22 patients able to be evaluated, pain intensity (visual analogue, 0-100 mm) at 9:00 a.m. and 4:00 p.m. was 31 +/- 23 and 28 +/- 18 mm, respectively, on PCI versus 28 +/- 18 and 27 +/- 17 mm, respectively, on CSCI [P = not significant (NS)]. The total dose of HM was 168 +/- 197 and 181 +/- 234 mg on PCI and CSCI, respectively (P = NS). No significant difference was found in nausea, drowsiness, or number of hours of sleep. The total number of extra doses of HM was 6 +/- 7 on CSCI versus 2 +/- 3 on PCI (P = .007). At the end of the study, patients chose PCI and CSCI in seven and 10 cases, respectively (P = NS; 5 patients expressed no preference). We conclude that both methods were similar in regard to effectiveness and toxic effects in short-term hospital use.

Developmental aspects of aging in women. A comparative study of dreams.

Changes with age in the nature of women's inner experience were investigated through a comparison of the manifest dreams of a group of older women (ages 40 to 85 years) with the dreams from two groups of younger women (ages 18 to 26 and 16 to 17 years). The major comparative findings include a narrowing down of internal personal investments, a decrease in concerns about aggression, a decrease in the dreamer's sense of herself as pivotal, and, strikingly, an augmented amount of internally represented robust and locomotor activity for the older women. These results seem to correspond with other reports in the literature on the experience of aging women.

Cortical motor activation patterns following hand transplantation and replantation.

We studied cortical activation patterns by functional MRI in a patient who received bilateral hand transplantation after amputation 6 years ago and in a patient who had received unilateral hand replantation within 2 hours after amputation. In the early postoperative period, the patient who had had the hand transplantation revealed strong activation of a higher motor area, only weak activation of the primary sensorimotor motor cortex and no activation of the primary somatosensory cortex. At 1-year follow-up, a small increase in primary sensorimotor motor cortex activation was observed. Activation of the primary somatosensory cortex was only seen at the 2 year follow-up. By contrast, after hand replantation, the activation pattern was similar to that of the uninjured hand within 6 weeks. This included activation of the primary sensorimotor motor cortex, higher motor areas and primary somatosensory cortex. Transplantation after long-standing amputation results in cortical reorganization occurring over a 2-year period. In contrast, hand replantation within a few hours preserves a normal activation pattern.

Learning complex arithmetic--an fMRI study.

Aim of the present functional magnet resonance imaging (fMRI) study was to detect modifications of cerebral activation patterns related to learning arithmetic. Thirteen right-handed subjects were extensively trained on a set of 18 complex multiplication problems. In the following fMRI session, trained and untrained problems (closely matched for difficulty) were presented in blocked order alternating with a number matching task and a fact retrieval task. Importantly, left hemispheric activations were dominant in the two contrasts between untrained and trained condition, suggesting that learning processes in arithmetic are predominantly supported by the left hemisphere. Contrasting untrained versus trained condition, the left intraparietal sulcus showed significant activations, as well as the inferior parietal lobule. A further significant activation was found in the left inferior frontal gyrus. This activation may be accounted for by higher working memory demands in the untrained as compared to the trained condition. Contrasting trained versus untrained condition a significant focus of activation was found in the left angular gyrus. Following the triple-code model [Science 284 (1999) 970], the shift of activation within the parietal lobe from the intraparietal sulcus to the left angular gyrus suggests a modification from quantity-based processing to more automatic retrieval. The present study shows that the left angular gyrus is not only involved in arithmetic tasks requiring simple fact retrieval, but may show significant activations as a result of relatively short training of complex calculation.

Efficacy and safety of a standardised 500 unit dose of Dysport (clostridium botulinum toxin type A haemaglutinin complex) in a heterogeneous cervical dystonia population: results of a prospective, multicentre, randomised, double-blind, placebo-controlled, parallel group study.

Results from a dose-ranging study in a selected group of de novo patients with rotational cervical dystonia (CD) suggest that 500 units of Dysport (Clostridium botulinum toxin type A haemaglutinin complex) is the optimal starting dose. The present study aimed to confirm the efficacy and safety profile of this dose in a population of CD patients more representative of those seen in a typical dystonia clinic. A total of 68 patients with moderate to severe CD (Tsui score > or = 9) were randomly assigned to receive placebo or Dysport 500 units. Treatment was administered according to the clinical pattern of head deviation, using a standardised injection protocol. A total of 21 patients (11 Dysport, 10 placebo) had not previously received botulinum toxin type A (BtxA) injections, and 47 patients (24 Dysport, 23 placebo) had received BtxA more than 12 weeks previously. Assessments were performed at baseline and weeks 4, 8 and 16. Patients defined as non-responders at week 4 were re-treated in an open phase with 500 units of Dysport at week 6, and were followed up at week 10. Significant between-group differences in Tsui scores were present at weeks 4 (p=0.001) and 8 (p=0.002). Similarly, there were significant between-group differences (p < 0.001) in patient and investigator assessments of response in favour of Dysport at weeks 4 and 8. Also, more Dysport (49%) than placebo (33%) patients were pain-free at week 4 (p=0.02). Overall, 30/35 (86 %) Dysport patients and 14/33 (42%) placebo patients were classified as responders at week 4. Adverse events were reported by 15/35 Dysport patients and 9/33 placebo patients. Open phase treatment produced improvements in Tsui (p < 0.001) and pain scores (p=0.011), and 23/24 patients were classified as responders. Although individual dose titration and muscle selection is desirable, this study demonstrated that a dose of 500 units of Dysport injected into clinically identified neck muscles without electromyographic guidance is safe and effective in the treatment of patients with the major clinical types of cervical dystonia.

A randomized double-blind crossover trial of intravenous lidocaine in the treatment of neuropathic cancer pain.

In a randomized, double-blind, crossover study, we evaluated the effect of intravenous lidocaine (5 mg/kg body weight over 30 min) on the neuropathic pain of advanced cancer patients. Pain intensity, assessed by a visual analogue scale, did not show any significant difference between lidocaine and placebo infusion. The blinded choice of patients and investigators also suggested no significant improvement from lidocaine when given by this regimen. Intravenous lidocaine does not appear to have a significant analgesic effect on neuropathic cancer pain.

Influence of the pain and symptom control team (PSCT) on the patterns of treatment of pain and other symptoms in a cancer center.

To assess the influence of a pain and symptom control team on the pattern of prescription of pharmacologic and nonpharmacologic treatments for cancer pain, we reviewed the charts of 100 consecutive patients admitted to the Cross Cancer Institute during 1987 and 100 patients admitted during 1984. The average daily dose of parenteral morphine per patient was 44 +/- 26 mg in 1987 versus 34 +/- 38 mg in 1984 (p less than 0.05). In 1987 and 1984, only 31 and 22% of the analgesics were ordered around the clock respectively (P:NS). Approximately half of the patients in 1987 and 1984 were prescribed antiemetics and two-thirds of the patients were prescribed laxatives. Parenteral narcotics were prescribed subcutaneously in 0/52 cases in 1984 versus 21/63 cases in 1987 (33%, p less than 0.01). The pattern of prescription of narcotics by residents changed significantly during the last four weeks of rotation as compared to the first four weeks. We conclude that there have been some changes in the modality of treatment of pain that are probably due to changes in the pattern of prescription by the residents and continued improvement in assessment of pain by nurses. However, in several areas of treatment the impact of a pain and symptom control team remains minimal.

Association between asthenia and nutritional status, lean body mass, anemia, psychological status, and tumor mass in patients with advanced breast cancer.

Sixty-four consecutive patients with advanced breast cancer were included in a study designed to determine the prevalence of asthenia and its association with other clinical features. The Asthenia Score (AS, the average of four tests designed by our group to assess asthenia) was 59 +/- 9 for patients versus 88 +/- 7 for a group of 68 normal controls (p less than 0.001). Twenty-six patients (41%) scored below the tenth percentile of normal controls and were considered asthenics. AS was correlated with depression and the general severity index of the SCL-90 R test. No association was found between AS and nutritional status, lean body mass, tumor mass, anemia, or type of treatment. We conclude that asthenia is a frequent symptom in patients with advanced breast cancer, which, in our series, showed independent correlations only with psychological distress.

The impact of a regional palliative care program on the cost of palliative care delivery.

In July 1995 the Edmonton Regional Palliative Care Program (ERPCP) was established in the City of Edmonton to increase the access of patients with terminal cancer to palliative care services, decrease the number of cancer deaths in acute-care facilities, and increase the participation of family physicians in the care of terminally ill patients. The objective of this retrospective study was to determine the cost of implementation of the ERPCP and savings in acute-care facility costs after its implementation. We did this by comparing the cost of care for patients during 1992-93 (prior to the ERPCP) and 1996-97 (with the ERPCP). The main outcome measures were the cost of care and the total hospital stay in days for all patients during their last acute-care hospital admission. The increased funding for the ERPCP was offset by a significant decrease in the overall cost of palliative care in the acute-care facilities. There was a substantial decrease in the palliative care costs in acute facilities from 11,963,846 dollars in 1992/93 to 3,449,055 dollars in 1996/97. This can be explained by the significant decrease in the number of palliative care patient days in acute-care facilities from 22,608 during 1992/93 to 6085 during 1996/97. Physician billings were slightly higher for 1996 as compared to 1992. In 1992, 90% (195,117/427,780) of the billings were made by the specialists (internists, surgeons, and other specialists), while in 1996/97 67% (359,869/537,342) of the payments were made to primary care practitioners (p < 0.0001). Overall, there were estimated saving of 1,650,689 dollars for palliative care costs in 1996/97 as compared to 1992/93. Our results suggest that the establishment of an integrated palliative care program reduced the cost of care. Prospective cost measurement studies are required.

Ego modalities in the manifest dreams of male and female Chicanos.

When the manifest dreams of young adult male and female Chicanos were examined through an inventory which captures the dream content and pattern, striking differences between male and female dreams were found in the areas of setting, characters, interaction, self, instinctual modalities, and realism. Generally speaking, the men's internal psychic world, as viewed through their dreams, tended to be organized around a highly visible and demarcated self seen as robustly active, randomly in motion, and often contentiously involved with unrelated others. The confines of this internal world were sketched in as broad, but were occupied by boundaries and barriers and were often subject to unpredictable events. In contrast, the women's internal world contained a relatively less sharply defined and less robustly active self, but also a less contentious self with a greater range of interactions with more, and more familiar characters. Narrower confines were matched by less emphasis on boundaries, greater predictability, and more goal-directed locomotion.

Dream patterns in Anglo and Chicano young adults.

This study is the conclusion of an exploratory cross-cultural investigation of dream content and organization. Following our report in "Ego Modalities in the Manifest Dreams of Male and Female Chicanos," (Brenneis and Roll, 1975), this paper examines differences in the organization and content of dreams: (1) between Anglo men and women; (2) between Anglo and Chicano men and Anglo and Chicano women; and (3) between Anglos and Chicanos.

Frequency of symptom distress and poor prognostic indicators in palliative cancer patients admitted to a tertiary palliative care unit, hospices, and acute care hospitals.

The Edmonton Regional Palliative Care Program was established to increase access to palliative care for terminal cancer patients in the region. Inpatient care is delivered, in decreasing order to distress, at the tertiary palliative care unit, by consult teams in acute care facilities, and in hospices. We reviewed the admission data for all patients discharged from the program between November 1, 1997, and October 31, 1998, in order to determine if demographical and clinical variables suggested appropriate use of the three levels of care. Patients admitted to the tertiary palliative care unit were significantly younger than those admitted to acute care of hospices (61 years versus 68 years and 71 years respectively, p < 0.0001), had a higher frequency of positive screening for alcoholism in the CAGE questionnaire (27% versus 16% and 14% respectively, p < 0.0001), and a higher frequency of poor prognostic pain syndromes as compared to acute care admissions (87% versus 65%, p < 0.0001). Overall, frequency of symptoms and severe symptoms was significantly higher in patients admitted to the palliative care unit than those admitted to the other two settings. Our results suggest that patients with demographic and clinical indications of higher distress are more frequently admitted to the tertiary palliative care unit. The clinical tools are useful predictors of utilization that can be used for monitoring health care delivery.

Predictors of home death in palliative care cancer patients.

With recent changes in health care there is greater emphasis on providing care at home, including the support of families to enable more home deaths. Since a home death may not be practical or desirable in every family situation, there is a need for an objective way to assess the viability of a home death in each individual family situation. The purpose of this study was to describe the relative role of predictors of home death in a cohort of palliative care patients with advanced cancer. A questionnaire was created as a means of assessing the viability of a home death. Five questions were included. Ninety questionnaires were administered by home care coordinators. A follow-up questionnaire was administered to record the place of death. Of the 73 evaluable patients, 34 (47%) died at home and 39 (53%) died in hospital or hospice. The desire for a home death by both the patient and the caregiver, support of a family physician, and presence of more than one caregiver were all significantly associated with a home death. Logistic regression identified a desire for home death by both the patient and the caregiver as the main predictive factor for a home death. The presence of more than one caregiver was also predictive of home death. The questionnaire is simple and, if our results are confirmed, it can be used for predicting those who will not have a home death.