EULAR revised recommendations for the management of fibromyalgia.

OBJECTIVE: The original European League Against Rheumatism recommendations for managing fibromyalgia assessed evidence up to 2005. The paucity of studies meant that most recommendations were 'expert opinion'. METHODS: A multidisciplinary group from 12 countries assessed evidence with a focus on systematic reviews and meta-analyses concerned with pharmacological/non-pharmacological management for fibromyalgia. A review, in May 2015, identified eligible publications and key outcomes assessed were pain, fatigue, sleep and daily functioning. The Grading of Recommendations Assessment, Development and Evaluation system was used for making recommendations. RESULTS: 2979 titles were identified: from these 275 full papers were selected for review and 107 reviews (and/or meta-analyses) evaluated as eligible. Based on meta-analyses, the only 'strong for' therapy-based recommendation in the guidelines was exercise. Based on expert opinion, a graduated approach, the following four main stages are suggested underpinned by shared decision-making with patients. Initial management should involve patient education and focus on non-pharmacological therapies. In case of non-response, further therapies (all of which were evaluated as 'weak for' based on meta-analyses) should be tailored to the specific needs of the individual and may involve psychological therapies (for mood disorders and unhelpful coping strategies), pharmacotherapy (for severe pain or sleep disturbance) and/or a multimodal rehabilitation programme (for severe disability). CONCLUSIONS: These recommendations are underpinned by high-quality reviews and meta-analyses. The size of effect for most treatments is relatively modest. We propose research priorities clarifying who will benefit from specific interventions, their effect in combination and organisation of healthcare systems to optimise outcome.

Irisin stimulates muscle growth-related genes and regulates adipocyte differentiation and metabolism in humans.

BACKGROUND: Irisin is a recently identified exercise-induced myokine suggested to induce browning of white adipocytes. Deficiency of myostatin, and thus stimulation of muscle growth, has also been reported to induce irisin and its precursor FNDC5 expression in muscle and drive the browning of white adipocytes in mice, implying that irisin may be related to muscle growth in addition to its beneficial effects in adipocytes. In humans, the effect of irisin in muscle hypertrophy as well as adipocyte metabolism has not been fully investigated. METHODS: Primary cultured human myocytes/adipocytes and 3T3-L1 cells were used to examine irisin-regulated gene/protein expression. Lipid accumulation, ATP content, glycolysis, lipolysis and metabolite profile were measured in control and irisin-treated (10 and 50 nM) adipocytes. RESULTS: In human myocytes, FNDC5 mRNA and irisin secretion were increased during myogenic differentiation, along with PGC1α and myogenin expression. Irisin treatment significantly increased insulin-like growth factor 1 and decreased myostatin gene expression through ERK pathway. PGC1α4, a newly discovered PGC1α isoform specifically related to muscle hypertrophy, was also upregulated. In human adipocytes, irisin induced uncoupling protein 1 and consequently increased adipocyte energy expenditure, expression of metabolic enzymes and metabolite intermediates, resulting in inhibition of lipid accumulation. Irisin and FNDC5 treatment also reduced preadipocyte differentiation, suggesting an additional mechanism in suppressing fat mass. CONCLUSIONS: These results suggest that irisin/FNDC5 has a pleiotropic role in muscle and improvement of adipocyte metabolism in humans.

Incidence, aetiology, and control of sternal surgical site infections.

BACKGROUND: Since sternal surgical site infections (SSIs) can be life-threatening, every effort should be made to reduce their rate of occurrence. AIM: To measure the rate of sternal SSIs after open heart surgery and to define the efficacy of infection control interventions in reducing this rate. METHODS: Surveillance of sternal SSIs was carried out prospectively for adult patients who underwent sternotomy between 2005 and 2012. Infection control interventions that were undertaken during the study period at different time intervals were prophylaxis with cefazolin or vancomycin, surveillance of sternal SSIs and feedback, preoperative nasal Staphylococcus aureus screening and decolonization with mupirocin, isolation of patients infected with or colonized by meticillin-resistant S. aureus, appropriate management of perioperative blood glucose level and chlorhexidine/alcohol usage for skin antisepsis. FINDINGS: There were 479 sternal SSIs in 18,460 patients during the study period (2.59%). The most frequent causes of sternal SSIs were coagulase-negative staphylococci (CoNS) (36%) and S. aureus (31%). Infection control interventions reduced the rate of sternal SSIs from 3.63% in 2005 to 1.65% in 2012 (P < 0.0001). CONCLUSION: Our study shows that the rate of sternal SSIs can be decreased with proper infection control interventions. However, the interventions that were undertaken were effective only in reducing the rate of sternal SSIs caused by S. aureus. It is time to find interventions to control sternal SSIs caused by CoNS, the pathogen responsible for most sternal SSIs in hospitals where S. aureus SSIs are successfully controlled.

Amylin-induced downregulation of hippocampal neurogenesis is attenuated by leptin in a STAT3/AMPK/ERK-dependent manner in mice.

AIMS/HYPOTHESIS: Both leptin and insulin sensitivity have been linked with pathophysiological processes involving the central nervous system in general, and the hippocampus in particular, but the role of leptin in hippocampal neurogenesis has not yet been elucidated. Also, no previous studies have evaluated whether amylin or the endogenous insulin sensitiser adiponectin interact with leptin to alter hippocampal neurogenesis in mouse hippocampal neuronal (HN) cells or investigated the role of leptin, amylin or adiponectin signalling in mouse HN cells. METHODS: Hippocampal neurogenesis and leptin, amylin and adiponectin signalling were studied in vitro using mouse H19-7 HN cell lines. RESULTS: Amylin decreased cell proliferation in a dose-dependent manner. This effect was diminished by leptin administration and was dependent on signal transducer and activator of transcription 3 (STAT3)/AMP-activated protein kinase (AMPK)/extracellular signal-regulated kinase (ERK). Adiponectin effects were null. We also observed, using immunocytochemical analysis, that amylin decreased activation of microtubule-associated protein 2, a specific neurite outgrowth marker, and synapsin, a specific synaptogenesis marker. By contrast, both effects were attenuated by co-administration of leptin. Finally, we observed that these effects were blocked by pre-treatment with AG490, a STAT3 inhibitor, and STAT3 small interfering RNA administration. CONCLUSIONS/INTERPRETATION: Our data suggest that amylin in pharmacological concentrations may have a neurotoxic effect whereas leptin in physiological and pharmacological concentrations has a protective effect counteracting amylin-decreased hippocampal neurogenesis via STAT3/AMPK/ERK signalling in mouse H19-7 HN cell lines. Overall, our data support a novel role for leptin and amylin in the processes of mouse hippocampal neurogenesis and provide new insights into the mechanisms of neurogenic regulation.

EULAR evidence-based recommendations for the diagnosis of hand osteoarthritis: report of a task force of ESCISIT.

OBJECTIVES: To develop evidence-based recommendations for the diagnosis of hand osteoarthritis (OA). METHODS: The multidisciplinary guideline development group, representing 15 European countries, generated 10 key propositions regarding diagnosis using a Delphi consensus approach. For each recommendation, research evidence was searched for systematically. Whenever possible, the sensitivity, specificity and likelihood ratio (LR) were calculated; relative risk and odds ratios were estimated for risk factors for hand OA. Quality of evidence was categorised using the European League Against Rheumatism (EULAR) hierarchy, and strength of recommendation was assessed by the EULAR visual analogue scale. RESULTS: Diagnostic topics included clinical manifestations, radiographic features, subgroups, differential diagnosis, laboratory tests, risk factors and comorbidities. The sensitivity, specificity and LR varied between tests depending upon the cut-off level, gold standard and controls. Overall, no single test could be used to define hand OA on its own (LR <10) but a composite of the tests greatly increased the chance of the diagnosis. The probability of a subject having hand OA was 20% when Heberden nodes alone were present, but this increased to 88% when in addition the subject was over 40 years old, had a family history of nodes and had joint space narrowing in any finger joint. CONCLUSION: Ten key recommendations for diagnosis of hand OA were developed using research evidence and expert consensus. Diagnosis of hand OA should be based on assessment of a composite of features.

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.

EULAR evidence based recommendations for the management of hand osteoarthritis: report of a Task Force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT).

OBJECTIVES: To develop evidence based recommendations for the management of hand osteoarthritis (OA). METHODS: The multidisciplinary guideline development group comprised 16 rheumatologists, one physiatrist, one orthopaedic surgeon, two allied health professionals, and one evidence based medicine expert, representing 15 different European countries. Each participant contributed up to 10 propositions describing key clinical points for management of hand OA. Final recommendations were agreed using a Delphi consensus approach. A systematic search of Medline, Embase, CINAHL, Science Citation Index, AMED, Cochrane Library, HTA, and NICE reports was used to identify the best available research evidence to support each proposition. Where possible, the effect size and number needed to treat were calculated for efficacy. Relative risk or odds ratio was estimated for safety, and incremental cost effectiveness ratio was used for cost effectiveness. The strength of recommendation was provided according to research evidence, clinical expertise, and perceived patient preference. RESULTS: Eleven key propositions involving 17 treatment modalities were generated through three Delphi rounds. Treatment topics included general considerations (for example, clinical features, risk factors, comorbidities), non-pharmacological (for example, education plus exercise, local heat, and splint), pharmacological (for example, paracetamol, NSAIDs, NSAIDs plus gastroprotective agents, COX-2 inhibitors, systemic slow acting disease modifying drugs, intra-articular corticosteroids), and surgery. Of 17 treatment modalities, only six were supported by research evidence (education plus exercise, NSAIDs, COX-2 inhibitors, topical NSAIDs, topical capsaicin, and chondroitin sulphate). Others were supported either by evidence extrapolated from studies of OA affecting other joint sites or by expert opinion. Strength of recommendation varied according to level of evidence, benefits and harms/costs of the treatment, and clinical expertise. CONCLUSION: Eleven key recommendations for treatment of hand OA were developed using a combination of research based evidence and expert consensus. The evidence was evaluated and the strength of recommendation was provided.

Sham interventions in randomized clinical trials of acupuncture--a review.

BACKGROUND AND OBJECTIVES: For non-drug interventions such as acupuncture, it is difficult to establish placebo or sham controls that are both inert and indistinguishable. We reviewed sham-controlled clinical trials of acupuncture to investigate (a) which types of sham interventions have been used in the past; (b) in what respects true and sham interventions differed; and (c) whether trials using different types of sham yielded different results. METHODS: 47 randomized controlled trials comparing true and sham acupuncture interventions for pain and a variety of other conditions were identified from systematic reviews and through a search in PubMed. Details of patients, interventions, sham interventions and outcomes were extracted in a standardized manner. RESULTS: In two trials the sham intervention consisted of superficial needling of the true acupuncture points, four trials used true acupuncture points which were not indicated for the condition being treated, in 27 trials needles were inserted outside true acupuncture points, five trials used placebo needles and nine trials used pseudo-interventions such as switched off-laser acupuncture devices. True and sham interventions often differed in a variety of other variables, such as manipulation of needles, depth of insertion, achievement of an irradiating needling sensation (de-chi), etc. There was no clear association between the type of sham intervention used and the results of the trials. CONCLUSION: Randomized trials investigating the specific effects of acupuncture have used a great variety of sham interventions as controls. Summarizing all the different sham interventions as "placebo" controls seems misleading and scientifically unacceptable.

Psychosocial function, clinical status, and radiographic findings in a group of chronic low back pain patients.

Low back pain is considered a problem with multiple facets for which the underlying causative factors should be determined. The aim of this study was to evaluate the relationships between depression, clinical status, and radiographic findings in a group of fifty patients with low back pain for more than 6 months. The patients underwent clinical examination and they completed Beck depression inventory (BDI), Aberdeen back pain scale (ABPS) and research questionnaire. Radiographic evaluations were performed. Clinical score and duration of symptoms were found to be positively correlated. The BDI scores were not found to be correlated with the existing variables. The ABPS scores were positively correlated with clinical scores and number of medications used.

Rehabilitation of flexor tendon injuries by use of a combined regimen of modified Kleinert and modified Duran techniques.

OBJECTIVE: Kleinert (active extension, rubber-band passive flexion) and Duran (passive extension, passive flexion) protocols are two basic types of early motion programs for rehabilitation of flexor tendon injuries. Researchers have been working on various modifications or combinations of these two protocols to improve rehabilitation results. The purpose of this study was to analyze the quality of the functional results of flexor tendon repair after a postoperative regimen of early mobilization by use of a combined regimen of modified Kleinert and modified Duran techniques. DESIGN: Thirty-seven patients (74 digits) with repaired flexor tendon injuries were treated. Functional results of the fingers were evaluated by the Buck-Gramcko system and total active motion measurements. RESULTS: The results were excellent in 73% of the fingers, good in 24%, fair in 1.5%, and none was rated poor. CONCLUSION: Our results are comparable with the previous studies that used various postoperative rehabilitation techniques. This postoperative management provides an effective way of achieving satisfactory results. Patient-assisted passive exercises are very safe and more cost effective than therapist-assisted passive exercises.

Bone mineral density in children with juvenile chronic arthritis.

The aim of this study was to evaluate bone mineral density changes in patients with juvenile chronic arthritis (JCA) and to determine the most likely causes of osteoporosis in these patients. Eighteen (11 male, 7 female) patients suffering from JCA and 14 healthy controls (10 male, four female) were included in this study. The mean age of the patients and control groups were 11.0 +/- 3.2 and 10.9 +/- 2.9 years respectively. Disease activity was determined by clinical and laboratory evaluation and 'Articular Disease Severity Score' (ADSS). Bone mineral density (BMD) of the femoral neck and lumbar spine was measured by dual photon absorptiometry. BMD of the patients at the lumbar spine was significantly lower than the control group (p < 0.05). This difference was more marked in patients treated with steroids. Femoral neck BMD was also lower in the patient group but this difference was not statistically significant. There was a negative correlation between ADSS and BMD at the spine. In conclusion, trabecular bone loss is characteristic for osteoporosis in JCA. Our results indicate that steroid treatment and disease severity are important factors in the development of osteoporosis in JCA.

The Turkish experience of poliomyelitis before and after a vaccination campaign.

It is very important that the poliovirus is eradicated as it has caused serious and permanent disabilities during the present century. In order to achieve success in the rehabilitation of poliomyelitis patients the role of vaccination compaigns as an essential part of preventive medical care should be appreciated. After every vaccination campaign successful results have been obtained. Thus we are optimistic that if these vaccination campaigns are carried out successful results will be achieved as was obtained after the 1985 vaccination campaign. As is understood from our report, according to the results of the 1985 vaccination campaign successful long-term results have been achieved. The results of the 1995 campaign will also be seen at a future date as this article does not report them. We appreciate the cooperation and support given by WHO during the staging of these campaigns.

Bowel dysfunction and irritable bowel syndrome in fibromyalgia patients.

Fibromyalgia and irritable bowel syndrome are both common conditions which account for most of the referrals to physical medicine and rehabilitation-rheumatology and gastroenterology clinics, and they frequently coexist. In this study, we utilized a previously validated questionnaire to assess the prevalence of symptoms of bowel dysfunction and irritable bowel syndrome, and to survey the range of bowel pattern in 75 patients with fibromyalgia as compared to 50 normal controls. Symptoms associated with irritable bowel syndrome (p < 0.05) were reported in 41.8% of the fibromyalgia patients and 16% of the normal controls. In conclusion, we found that patients with fibromyalgia have a high prevalence of gastrointestinal complaints confirming the results indicating that fibromyalgia and irritable bowel syndrome frequently coexist. This may suggest a common pathogenic mechanism for both conditions.

Etiological and functional evaluation of the pediatric population with spinal cord injuries.

Spinal cord lesions are the result of many etiological factors and are associated with motor, sensorial and autonomic dysfunctions. The subjects evaluated were a total of 217 paraplegics and quadriplegics who had been enrolled in a rehabilitation program during the last five years conducted by the Department of Physical Medicine and Rehabilitation of the Hacettepe University Faculty of Medicine. Forty-three of these patients were in the pediatric age group. In this clinical trial, the patients with spinal cord injuries were examined according to their age, sex, etiological factors and functional status. Frankel's scale was used for functional assessment. The mean age of patients was 9.19 +/- 4.19 years and varied between 1-16 years. The results of our classification according to etiological factors were as follows: Nineteen patients with tumors (44.1%), nine patients with infections (20.93%), five patients with congenital abnormalities (11.63%), five patients with vascular lesions (11.63%), four patients with trauma (9.30%), and one patient with a degenerative central nervous system disorder (2.32%). The effect of the rehabilitation program on the functional status of the patients is discussed.

Results of the combined treatment of paediatric intraspinal tumours.

In this article 98 patients with paediatric intraspinal tumours are presented. All were evaluated according to their ages, sex, signs and symptoms. The patients also had radiological and histopathological studies; and the results of surgical, physical medicine and rehabilitation and of radiotherapy are discussed and compared with the results of patients reported in the literature.

Traumatic spinal cord injuries in Turkey.

Spinal cord lesions have various aetiologies, and trauma is one of the leading causes. Patients with spinal cord injuries (SCI) often have motor, sensory and autonomic dysfunctions and require a multidisciplinary rehabilitation programme. In this study 1694 SCI patients were investigated, including the frequency, and the distribution by age, sex, profession, aetiology, clinical status and year of occurrence. Traumatic SCI is more frequent among males than females and among those between the ages of 15 and 39 years. Regarding the aetiology, traffic accident comprised 35.41% of the total cases, the second most common cause was falls with 29.51%, and the third was high velocity bullet wounds: 21.95%.

Diagnosis and treatment of intraspinal lipomas.

In this article a 32-case series of intraspinal lipoma localized to the lumbosacral region is presented. All of the patients underwent surgery. Recent reports in the literature indicate that although these lesions show advanced and progressive neurological deficits, very good results can be achieved with surgical treatment. The advantages of computed tomography in diagnosis and the importance of early surgical intervention and postoperative rehabilitation are emphasized.

Maternal hair zinc concentration in neural tube defects in Turkey.

Hair zinc concentration was measured in samples taken from 57 mothers who delivered infants with neural tube defects (NTD) (mainly anencephaly). Control groups consisted of 30 healthy mothers with normal offspring and 37 nonpregnant women from middle-income backgrounds. Zinc concentration was also measured in the hair of eight infants with NTD (four being anencephalic). The mean maternal hair zinc concentration in the NTD group (128.2 +/- 38.9 micrograms/g) was lower than that of the control women (p less than 0.001), whereas the mean hair zinc level of malformed babies (250.4 +/- 85.2 micrograms/g) was significantly higher than that of normal infants (193.4 +/- 39.2 micrograms/g) (p less than 0.05). Maternal nutritional zinc deficiency was thought to be one of the factors responsible for NTD in Turkey.