EULAR evidence-based recommendations for the management of fibromyalgia syndrome.

OBJECTIVE: To develop evidence-based recommendations for the management of fibromyalgia syndrome. METHODS: A multidisciplinary task force was formed representing 11 European countries. The design of the study, including search strategy, participants, interventions, outcome measures, data collection and analytical method, was defined at the outset. A systematic review was undertaken with the keywords "fibromyalgia", "treatment or management" and "trial". Studies were excluded if they did not utilise the American College of Rheumatology classification criteria, were not clinical trials, or included patients with chronic fatigue syndrome or myalgic encephalomyelitis. Primary outcome measures were change in pain assessed by visual analogue scale and fibromyalgia impact questionnaire. The quality of the studies was categorised based on randomisation, blinding and allocation concealment. Only the highest quality studies were used to base recommendations on. When there was insufficient evidence from the literature, a Delphi process was used to provide basis for recommendation. RESULTS: 146 studies were eligible for the review. 39 pharmacological intervention studies and 59 non-pharmacological were included in the final recommendation summary tables once those of a lower quality or with insufficient data were separated. The categories of treatment identified were antidepressants, analgesics, and "other pharmacological" and exercise, cognitive behavioural therapy, education, dietary interventions and "other non-pharmacological". In many studies sample size was small and the quality of the study was insufficient for strong recommendations to be made. CONCLUSIONS: Nine recommendations for the management of fibromyalgia syndrome were developed using a systematic review and expert consensus.

Calcium ionophore-induced de-encryption of tissue factor in monocytes is associated with extensive cell death.

INTRODUCTION: Cell surface tissue factor (TF) is normally encrypted, but can be activated by various cellular perturbations. Exposure of TF bearing cells to calcium ionophore has been reported to increase TF activity, de-encrypt TF, by phosphatidylserine (PS)-dependent and -independent mechanisms. Our aim has been to examine at the single cell level, if increased cell surface PS coincided with increased cell surface TF antigen, and cell death (necrosis, 7-AAD-intercalation), and relate this to monocyte- and microparticle (MP)-associated procoagulant activity. MATERIALS AND METHODS: We exposed lipopolysaccharide-stimulated, human, elutriation-purified, cryopreserved TF bearing monocytes to increasing concentrations of calcium ionophore (A23187) and measured procoagulant activity in cells and supernatants. These measurements were compared with quantification of cell surface TF and PS (Annexin V) and of cell necrosis (7-AAD) by flow cytometry, and complemented by confocal microscopy. RESULTS: We observed that calcium ionophore increased cellular and MP-associated TF activity, but not cell surface TF antigen. The discrepancy between TF activity and TF antigen coincided with a dose-dependent increase in the number of cells expressing PS. These cells were to a large extent necrotic and many of them also expressed TF. CONCLUSIONS: We suggest such TF positive dying cells to contribute to the discordance between TF activity and TF expression. Calcium ionophore also increased MP-associated TF activity and release of MPs may be a way to disseminate procoagulant activity. Our findings emphasize the importance of adequately assessing cell death and taking into consideration its possible role in experiments with calcium ionophore.

The use of CellaVision™ DM96 in the verification of the presence of blasts in samples flagged by the Sysmex XE-5000.

INTRODUCTION: The CellaVision™DM96 is a digital pattern recognition system that classifies white blood cells. The aim of this study was to evaluate whether the CellaVision preclassification feature, without a subsequent re-classification, was a sufficient approach to follow up flags reported by Sysmex XE-5000. METHODS: Pairs of blood smears from 400 samples reported with suspect flags were examined using conventional microscopy and the CellaVision features. The effect of pre- vs. re-classification, and intersmear and between-technologist variation, on blast counts was assessed using generalized linear mixed models (GLMM). RESULTS: The GLMM analysis showed a significant difference between the blast counts of preclassification vs. re-classification (P = 0.009). The analysis showed no significant difference between duplicate smears (P = 0.621) or between technologists (P = 0.542). Preclassification showed blasts in 105 samples (26%), where the re-classification feature did not detect any blasts. Not a single sample that was re-classified as positive for blasts was preclassified as negative. Compared to manual microscopy, the sensitivity and specificity of the preclassification feature were 0.83 and 0.66, respectively. CONCLUSION: The preclassification feature alone is sufficient to verify the absence of blasts in flagged samples. When the preclassification feature detects blasts, the finding has to be verified or reclassified by an experienced technologist. However, the use of CellaVision™DM96 in the follow-up of blast reports has to be questioned due to the finding of false-negative samples in the preclassification feature, but also after re-classification, compared to manual slide review.

Women with fibromyalgia: work and rehabilitation.

PURPOSE: To explore disability in women with fibromyalgia with a focus on their work situation. METHOD: Review of literature on work status of women with fibromyalgia. RESULTS: Major differences exist between studies in reported disability and in the percentages of women working. Limitations caused by pain, fatigue, decreased muscle strength, and endurance influence work capacity. However, 34 - 77% of the women work. Individual adjustments in the work situation are reported. When the women find a level that matches their ability, they continue to work and find satisfaction in their work role. Many factors besides degree of impairment or disability influence whether clients with longstanding pain can remain in their work role or return to work after sickness leave. CONCLUSION: The total life situation, other commitments, type of work tasks, the ability to influence the work situation, and the physical and psychosocial work environment are important factors in determining whether a person can remain in a work role. More knowledge is needed about how to adjust work conditions for people with partial work ability to the benefit of society and the individual.

Living with fibromyalgia. Consequences for everyday life.

The influence of chronic pain on daily life was studied in 58 patients (55 women and three men) with fibromyalgia. The mean age was 45 +/- 11 (SD) years. A mail questionnaire including a 2-day diary was used for data collection. Information was gathered on social background, employment status, symptoms, physical training habits, patients' experience of general health, physical condition, and difficulties in performing motor tasks. The patient reported every half hour in the activity diary the degree of pain and fatigue, whether the activities were difficult to perform, and whether the patient considered them to be enjoyable, valuable, and meaningful. Fifty-five percent of the group had gainful employment. Most were working shorter hours and with changed work tasks. Motor tasks, such as carrying, holding, and running were more difficult to perform than before the onset of the symptoms, and half of the group reported most of their activities as strenuous to perform. Thirty-nine persons (67%) reported no, or very short, pain-free periods during the 2 days. In conclusion, symptoms influenced daily life considerably, and almost all patients reported changes in habits and routines as a consequence of fibromyalgia. An assessment of the patient's total life situation gives valuable information for understanding the patients' ability to handle everyday life.

Impact of fibromyalgia on everyday life: a study of women in the USA and Sweden.

The study investigated how 39 women with fibromyalgia (FM), living in two countries (USA or Sweden), report the consequences of fibromyalgia on everyday life activities. Data were collected using questionnaires, diaries and interviews. The result showed that the impact on everyday life was considerable. The majority of the women experienced pain and fatigue for more than 90% of their time awake. There were no significant differences between the national groups in time use, problems with everyday activities, or quality of life. Overall, the differences between individuals were greater than between the national groups. The majority of the employed patients in the Swedish group had reduced their working time, while the employed patients in the USA group worked mainly full-time. Patients who were able to reduce their working hours to fit their perceived capacity were less exhausted during their leisure, and reported higher satisfaction with daily activities.

The rehabilitation process for the geriatric stroke patient--an exploratory study of goal setting and interventions.

PURPOSE: The aim was to describe and analyse the rehabilitation process of the geriatric stroke patient from two perspectives; the treatment goals expressed by the staff and the patient and the treatment interventions chosen by the physiotherapist and occupational therapist. A secondary aim was to test whether the process, treatment goals and interventions could be classified according to the International Classification of Impairments, Disabilities and Handicaps (ICIDH). METHOD: Qualitative interviews were performed with patients and personnel; diaries were used to register treatment interventions. The 30 interviews were categorized according to the goals expressed by physiotherapists, occupational therapists, physicians and patients. The diaries (n = 22) were analysed to describe how treatment interventions were connected in time, at what levels (impairment, disability and handicap) the interventions were directed, and finally, whether certain decisions were made in order to change the rehabilitation process. RESULTS: The patients talked more about attaining their pre-stroke status than about their goals. The therapists set goals according to functional level, whereas the doctors expressed themselves in general terms. Three patterns of rehabilitation processes were found: one with clearly identified decision points, one with a set programme which was not changed through the process, and one where the goal was changed according to changes in medical status. CONCLUSIONS: The patient does not participate in the goal-setting process, and the vaguely expressed goals are not measurable. The rehabilitation process and reason for discharge demonstrate different patterns. Treatment interventions, if related to the ICIDH, give a clear picture of the process, though certain interventions do not fit in the classification.

Amphetamine as a protective agent against oxygen-induced convulsions in mice.

Male mice exposed to hyperbaric oxygen (HBO) at 4.5 ATA O2 exhibit a number of toxic symptoms including convulsions, diminished respiration and an acoustic reaction controlled by the central nervous system. To study whether stimulation of the nervous system could offer protection against the convulsions, mice were injected i.p. with various doses of d-amphetamine before HBO. At a dose of 1.0 mg X kg-1 of d-amphetamine the mice could stay at 5 ATA O2 without convulsions about three times as long as those injected with saline only. At high doses, 4 and 8 mg X kg-1, there was a weak protective effect or the time to convulsions was shortened. Amphetamine increases the release of dopamine in the brain and it is possible that the mechanisms of protection against HBO induced convulsions are involved in that process. The degree of protection, however, depends on the dose; therefore, it also is supposed that amphetamine in low doses acts on the autoreceptors with a presynaptic effect, which in this case is protective against the convulsions without affecting the respiration.

Use of a tamponade catheter in the bleeding nephrostolithotomy track.

Bleeding from the nephrostomy track, which is the most common major complication of percutaneous extraction of renal stones, was treated in 5 patients with the Kaye double-lumen nephrostomy tamponade catheter. This treatment was effective in all cases. The procedure eliminates the need for more invasive measures like embolisation and open surgery with renal resection, both of which cause loss of functioning renal parenchyma.

Outpatient-based extracorporeal shock wave lithotripsy using EDAP LT-01.

Between March 1988 and March 1990, 751 patients were treated with shock wave lithotripsy using EDAP LT-01. Six hundred and eight patients had renal stones while 143 patients had stones located in the ureter. Because of difficulties in locating ureteric stones with ultrasound 92% of them were pushed back to the kidney before treatment. The mean stone size was 10 mm, range 4-30 mm. Patients with stones bigger than 15 mm had a double J-stent placed before treatment. The mean number of treatments per patient was 1.7 (range 1-8). Sixty-six per cent of the patients with renal stones were completely stone-free after ESWL monotherapy. Another 5% became stone-free after auxiliary procedures in the ureter, because of retained fragments. Fragments equal to or less than 4 mm were retained in 14% of the patients with the renal stones. Of the patients with ureteric stones mobilised back to the kidney 95% were rendered stone-free after ESWL. Most patients experienced no or very little discomfort during the treatment and only 29% of them received analgesics. General of epidural anaesthesia was given to 1% of the patients. Because of the low demand for analgesia or anaesthesia, 99% of the patients with renal stones were treated on an outpatient basis. During the second year, 74% of the patients with ureteric stones were treated on an outpatient basis.

Anticoagulant effects of an antidiabetic drug on monocytes in vitro.

INTRODUCTION: Monocyte- and microparticle (MP)-associated tissue factor (TF) is upregulated in diabetes. Lipopolysaccharide (LPS) induces expression of TF and alternatively spliced TF (asTF) and increases MP release from monocytes. Using LPS-stimulated TF-bearing human monocytes, we examined whether glibenclamide, a sulfonylurea used to treat diabetes type 2, might possess anticoagulant properties. METHODS: We studied the effects of glibenclamide on cell- and supernatant-associated procoagulant activity (Factor Xa-generating assay and clot formation assay), on expression of TF and asTF (flow cytometry, RT-qPCR, western blot) and on cell viability and MP release (flow cytometry). RESULTS: Glibenclamide dose-dependently decreased procoagulant activity of cells and supernatants. The reduction in cellular procoagulant activity coincided with reduced expression of TF and asTF in cells, whereas cell viability remained almost unchanged. The glibenclamide-induced reduction in procoagulant activity of supernatants appeared to be associated with a decreased number of released MPs. CONCLUSIONS: Reduction of monocyte- and supernatant-associated procoagulant activity by glibenclamide is associated with decreased expression of TF and asTF and possibly with a reduced MP number. Our data indicate that glibenclamide reduces the prothrombotic state in LPS-stimulated monocytes in vitro. Glibenclamide might therefore also have an anticoagulant effect in vivo, but this needs to be further evaluated.

Patients' and relatives' thoughts and actions during and after symptom presentation for an acute myocardial infarction.

BACKGROUND: Relatives play an important role in deciding to seek medical care after the onset of symptoms of an acute myocardial infarction (AMI). OBJECTIVE: The aim of this study was to gain deeper understanding of how AMI patients and their relatives think and act during and after onset of symptoms. METHODS: Six focus group interviews were conducted with AMI patients (N=13) and relatives (N=14). Manifest content analysis was used to analyse the transcribed data. RESULTS: The AMI patients experienced a variety of symptoms and both patients and relatives often felt uncertain about the origin of the symptoms, interpreted them as less serious conditions and tried to alleviate the discomfort in various ways. When symptoms continued the patients consulted a relative, who often decided to seek care. Many considered waiting for an ambulance was too long and the relative often drove the patients to the hospital. CONCLUSION: Patients as well as relatives were insecure about AMI symptoms and how to act. All patients contacted a relative, who was more eager than the patient to seek help. Many preferred to go in their own car to the hospital, believing it to be faster than an ambulance. Information about AMI symptoms and recommended action should be given to the public and to AMI patients and their relatives.

Repeated isologous transplantation of islets of Langerhans in the diabetic rat.

The metabolic response to repeated isologous transplantation of isolated pancreatic islets was studied in 11 streptozotocin-diabetic AGUS rats. The islets were isolated with collagenase and transplanted intra-portally in batches previously found to be quantitatively insufficient for reversal of the diabetic state. Primary transplantation caused a slight improvement whereas retransplantation with the same number of islets three weeks later was followed by normalization of blood glucose, plasma insulin, urine volume and urine glucose per 24 hours during a three-month observation period. Repeated isologous transplantation of isolated pancreatic islets has an additive effect on the metabolism in that two insufficient tissue doses correct streptozotocin induced diabetes in the rats.

Transplantation of isolated pancreatic islets: current status and prospects.

Complete and permanent reversal of diabetes by transplantation of isolated pancreatic islets has been repeatedly demonstrated experimentally, whereas islet isolation and transplantation in man are associated with largely unsolved problems: the standard isolation procedure including disruption of acini and collagenase digestion is ineffective. Improvement of the islet yield is currently obtained in animal and human trials by using substances selectively acting on exocrine tissue and others protecting the islets at the isolation as well as in tissue culture media. Islet tissue banks and repeated transplantations seem to be realistic also in man. Islets are advantageously implanted intraportally in the liver. They are rejected soon without protection or efficient immunosuppression. Intense research concerns islet-containing diffusion chambers, macrophage suppression, new immunosuppressive agents and induction of immunological tolerance. A successful solution of the technical and immunological problems will aggravate a shortage of donor tissue, already noticeable in the experimental work: this will make the recipient selection crucial.

Living with continuous muscular pain--patient perspectives. Part I: Encounters and consequences.

The purpose of the present study was to focus on the patient perspectives of living with chronic muscular pain, and to identify factors that can explain and give further understanding of how the condition influences everyday life. Forty women with fibromyalgia, living in two different cultural, health care and social security settings, Sweden and the USA, were interviewed, using a semi-structured format. Three preliminary typologies are suggested for further studies: Encounters, Consequences, and Strategies. The study is presented in two articles: Part I: Encounters and consequences, Part II: Strategies for daily life. This first article shows that the contradiction between the patients' perception of illness and the lack of objective findings is stressful. The women feel rejected, misunderstood, and disbelieved, which prevents them from dealing with their situation constructively. Long investigation periods provoke anxiety, and confirmation of the diagnosis is a relief. Daily routines are disrupted, conflicts between life roles lead to additional stress and the women experience loss of ability to perform valued activities, lack of physical fitness and loss of future opportunities. Patients need early and adequate information and the consequences of the condition must be acknowledged and taken into consideration if secondary economic and psychosocial consequences are to be minimized.

Living with continuous muscular pain--patient perspectives. Part II: Strategies for daily life.

This second article of the study Living with Continuous Muscular Pain is Part II: Strategies for Daily Life. The primary purpose was to explore, analyse and describe how women with fibromyalgia, living in two different cultural, health care and social security settings, managed their everyday life in spite of the limitations imposed by the condition. Data were collected through qualitative semi-structured interviews with 40 women, 20 living in the USA and 20 in Sweden. The different strategies used by the women were identified and a preliminary typology of strategies is proposed as a base for further and more specific studies. The results support earlier findings, though the qualitative approach adds knowledge regarding the women's own perception, interpretation and experiences of how to deal with the problems that arose. The findings in the two national groups were very similar, but differences in the medico-legal compensation systems influenced the women's opportunities to reduce working hours. Changes of habits, roles and lifestyle, as well as ergonomic considerations were required. These changes take time and require continued support from the environment and the health care providers. Further insight into the consequences of the condition is necessary for the planning of successful treatment and support programs.

Longterm effects of fibromyalgia on everyday life. A study of 56 patients.

Fifty-six patients with fibromyalgia, previously studied in 1984, were followed up after five years, using a mail questionnaire and a global health assessment instrument, the Sickness Impact Profile. The aim was to investigate the patients' perception of their symptoms and to describe the consequences for everyday life. Half of the patients reported that pain, fatigue and sleep problems had increased, less than 20% reported improvements, and 30-40%, no change. In spite of this, 25% reported that their overall condition had improved. Motor tasks were somewhat less difficult to manage. The symptoms had severe consequences for the patients' ability to manage everyday life activities. The study confirms that fibromyalgia, once established, is a non-remitting syndrome. Also, the social consequences were constant over time.

Factors of importance for work disability in women with fibromyalgia.

OBJECTIVE: To identify factors of importance for women with fibromyalgia (FM) to continue working despite the limitations imposed by the symptoms. METHODS: A mail questionnaire with questions regarding social background, symptoms, sickness benefits, work situation, work conditions and adjustments, opinions regarding own work ability, and satisfaction with the situation was sent to 218 consecutive women seen at a university pain or rheumatology clinic. Answers were obtained from 176 women. RESULTS: Pain, poor quality sleep, abnormal tiredness, muscle stiffness, and increased pain after muscle exertion were frequently reported symptoms. Fifty percent of the women were employed, 15% full-time. Twenty-three percent reported FM as the reason for not working. The work situation had been changed for 58% of the working women, and 80% counted on being able to continue working. CONCLUSION: Work disability is a serious concern in FM, and the majority of women with FM have limitations in their ability to work. Our results indicate that individual adjustments in the work situation need to be made and that women who have found a level matching their ability may continue to work and find it satisfactory. Early intervention in the work situation is recommended.