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.

The synergistic activity of tiamulin and chlortetracycline: in-feed treatment of bacterially complicated enzootic pneumonia in fattening pigs.

The antibacterial effects of a combination of tiamulin and chlortetracycline in vitro against a number of field isolates of Pasteurella multocida, Haemophilus pleuropneumoniae and Bordetella bronchiseptica were examined. There was a marked synergism between the two antibiotics against all eight isolates of P multocida, against seven of nine isolates of H pleuropneumoniae and against the single strain of B bronchiseptica tested. Two field trials were carried out on a herd with a history of complicated enzootic pneumonia where the presence of Mycoplasma hyopneumoniae and P multocida had been established and subsequently the presence of H pleuropneumoniae was discovered. Feed containing tiamulin at 100 ppm combined with chlortetracycline at 300 ppm was given for seven days to pigs affected with pneumonia, and the results were compared with untreated controls and pigs receiving chlortetracycline at 300 ppm. There was a follow-up observation period of three weeks when all groups received unmedicated feed. During the medication period the combination treated groups showed a statistically significant increase in average daily weight gain of 156 g (20.4 per cent) and in feed conversion efficiency of 0.576 (20.8 per cent) and a numerical improvement in average disease score in comparison with the untreated controls. These improvements were approximately double those observed in the groups treated with 300 ppm chlortetracycline which showed improvements of 93 g (12.2 per cent) in average daily gain and 0.301 (10.9 per cent) in feed conversion efficiency. During the following three weeks most of the initial gains were lost, probably owing to the reinfection of the treated groups by the untreated controls.

A comparison of thalidomide and pentobarbital - new methods for identifying novel hypnotic drugs.

We have compared the sleep-producing effects of thalidomide and pentobarbital. In a dose range that did not produce ataxia, thalidomide increased slow wave sleep and rapid eye movement sleep in cats (2-8 mg/kg p.o.) and rats (16 mg/kg p.o.). Pentobarbital had hypnotic activity in the same dose range but produced ataxia also at these doses. Thalidomide reduced spontaneous activity of both mice and rats. This occurred over a dose range of 8 to 1000 mg/kg p.o., but plateaued at a level of activity well above the complete inactivity of anesthesia that occurred with pentobarbital at well above the complete inactivity of anesthesia that occurred with pentobarbital at doses (greater than or equal to 32 mg/kg p.o.) above the hypnotic range. Several simple screens for thalidomide-like activity have been described which, together, could facilitate the search for thalidomide-like hypnotics. Pentobarbital, at doses 3 to 10 times the hypnotic range, prevented audiogenic seizures in physically dependent rats withdrawn from sodium barbital but thalidomide did not substitute for barbiturates even at doses 30 times those that increased sleep. Thalidomide, but not pentobarbital, enhanced the sleep-producing effect of electrical stimulation of basal forebrain in cats. The latter two findings suggest that thalidomide probably has a mechanism of action different from that of pentobarbital and that this may involve the activation of a sleep center in the forebrain.