Altered fMRI resting-state connectivity in individuals with fibromyalgia on acute pain stimulation.

BACKGROUND: Fibromyalgia is a chronic widespread pain condition, with patients commonly reporting other symptoms such as sleep difficulties, memory complaints and fatigue. The use of magnetic resonance imaging (MRI) in fibromyalgia has allowed for the detection of neural abnormalities, with alterations in brain activation elicited by experimental pain and alterations in resting state connectivity related to clinical pain. METHODS: In this study, we sought to monitor state changes in resting brain connectivity following experimental pressure pain in fibromyalgia patients and healthy controls. Twelve fibromyalgia patients and 15 healthy controls were studied by applying discrete pressure stimuli to the thumbnail bed during MRI. Resting-state functional MRI scanning was performed before and immediately following experimental pressure pain. We investigated changes in functional connectivity to the thalamus and the insular cortex. RESULTS: Acute pressure pain increased insula connectivity to the anterior cingulate and the hippocampus. Additionally, we observed increased thalamic connectivity to the precuneus/posterior cingulate cortex, a known part of the default mode network, in patients but not in controls. This connectivity was correlated with changes in clinical pain. CONCLUSIONS: These data reporting changes in resting-state brain activity following a noxious stimulus suggest that the acute painful stimuli may contribute to the alteration of the neural signature of chronic pain. WHAT DOES THIS STUDY/ADD?: In this study acute pain application shows an echo in functional connectivity and clinical pain changes in chronic pain.

Resting state connectivity correlates with drug and placebo response in fibromyalgia patients.

Fibromyalgia is a chronic pain syndrome characterized by widespread pain, fatigue, and memory and mood disturbances. Despite advances in our understanding of the underlying pathophysiology, treatment is often challenging. New research indicates that changes in functional connectivity between brain regions, as can be measured by magnetic resonance imaging (fcMRI) of the resting state, may underlie the pathogenesis of this and other chronic pain states. As such, this parameter may be able to be used to monitor changes in brain function associated with pharmacological treatment, and might also be able to predict treatment response. We performed a resting state fcMRI trial using a randomized, placebo-controlled, cross-over design to investigate mechanisms of action of milnacipran (MLN), a selective serotonin and norepinephrine reuptake inhibitor (SNRI), in fibromyalgia patients. Our aim was to identify functional connectivity patterns at baseline that would differentially predict treatment response to MLN as compared to placebo. Since preclinical studies of MLN suggest that this medication works by augmenting antinociceptive processes, we specifically investigated brain regions known to be involved in pain inhibition. 15 fibromyalgia patients completed the study, consisting of 6 weeks of drug and placebo intake (order counterbalanced) with an interspersed 2 week wash out period. As a main finding we report that reductions in clinical pain scores during MLN were associated with decreased functional connectivity between pro-nociceptive regions and antinociceptive pain regions at baseline, specifically between the rostral part of the anterior cingulate cortex (ACC) and the insular cortex (IC), as well as between the periaqueductal gray (PAG) and the IC: patients with lower preexisting functional connectivity had the greatest reduction in clinical pain. This pattern was not observed for the placebo period. However a more robust placebo response was associated with lower baseline functional connectivity between the ACC and the dorsolateral prefrontal cortex. This study indicates that ACC-IC connectivity might play a role in the mechanism of action of MLN, and perhaps more importantly fcMRI might be a useful tool to predict pharmacological treatment response.

Hypotension and eosinophilia with atorvastatin.

A case report of a 67-year-old man who suffered a hypersensitivity reaction to atorvastatin is described. He suffered collapse and was in shock characterised by marked hypotension, facial oedema and eosinophilia. His initial condition led the surgeons to think he might have had an abdominal sepsis. The reaction with angio-oedema reoccurred on rechallenge. The literature on statin hypersensitivity reactions which can occur several months after commencing therapy is reviewed. Although the estimated prevalence is rare (0.1%), prescribers and pharmacists should be aware of this important reaction which can be quite debilitating.

A systematic review of drug induced ocular reactions in diabetes.

AIMS: To conduct a systematic review of drug induced adverse ocular effects in diabetes to determine if this approach identified any previously unrecognised adverse drug effects; to make a preliminary assessment of the feasibility of this approach in identifying adverse drug reactions; and to assess the current accessibility of this information to prescribing physicians. METHODS: Literature search of online biomedical databases. The search strategy linked eye disorders with adverse drug reactions and diabetes. Source journals were classified as medical, pharmaceutical, diabetes related, or ophthalmological. It was determined whether the reactions identified were recorded in drug datasheets and the British National Formulary. RESULTS: 63 references fulfilled the selection criteria, of which 45 were considered to be relevant to the study. The majority of these were case reports but cross sectional surveys, case-control and cohort studies, and review articles were also identified. 61% of the reactions were not recorded in the British National Formulary and 41% were not recorded in the datasheets. 55% appeared in specialist ophthalmology journals. CONCLUSIONS: This is a feasible approach to the identification of adverse drug reactions. Adverse reactions not listed in the most commonly used reference sources were found. The majority were published in specialist ophthalmology journals which might not be seen by prescribing physicians.

Shared care: a review of the literature.

This review examines broad issues of concern regarding the primary/secondary care interface. The main purpose was to identify areas of good practice which could be adapted for more general use. One of the most fundamental aspects identified was communication, which is discussed in some detail. Also covered are shared prescribing and disease management. The data suggest that the most effective system(s) of shared care has yet to be established. Further qualitative and economic evaluations are required, taking into account patient preferences. Although the literature does describe certain practice exemplars, it is clear that inter- and intra-professional communication continues to be a problem. Whilst information technology may provide some of the solutions, it is concluded that a culture change, which compels health professionals to make sharing of patient information a much higher priority, is required.

A survey of the prevalence of penicillin-specific IgG, IgM and IgE antibodies detected by ELISA and defined by hapten inhibition, in patients with suspected penicillin allergy and in healthy volunteers.

1. IgG, IgM and IgE anti-benzylpenicilloyl (BPO) antibody activities were determined by enzyme-linked immunosorbent assay (ELISA) in sera from 100 patients who claimed to be allergic to penicillin, and from 50 healthy volunteers. Continuous frequency distributions for all three classes of anti-BPO antibody, defined as differential binding (delta OD) to BPO-human serum albumin (HSA) and HSA, were obtained for both groups. 2. For IgM and IgE classes the anti-BPO activities were slightly but statistically significantly higher in the patient group compared with the volunteer group. 3. Hapten inhibition ELISAs were performed to confirm specificity for the BPO determinant. On the basis of antibody activities (delta OD values) greater than or equal to 0.3 and 50% inhibition of binding in the presence of 100 micrograms ml-1 BPO-caproate, BPO-specific IgG antibody was identified in 4/100 of the patients' sera and in 1/50 of the volunteers' sera; BPO-specific IgM was identified in 7/100 patients' sera and 1/50 volunteers' sera; and BPO-specific IgE in 5/100 patients' sera and 1/50 volunteers' sera. 4. Not all sera with differential antibody binding to BPO-HSA/HSA were inhibited by the BPO hapten. Hence, hapten inhibition assays are essential for the unambiguous demonstration of drug specific antibodies.

Antibiotic costs and prescribing patterns in a recently commissioned Liverpool teaching hospital. Part I: Antimicrobial therapy.

All antibiotics prescribed in a major teaching hospital were prospectively surveyed during 31 consecutive days. Of 2350 patients admitted during that period, 577 (24.6%) received antibiotics, 238 (10.1%) for prophylaxis and 417 (17.7%) for treatment. A total of 483 infections occurred in the treated patients, mainly in the chest (33.9%) and urinary tract (27.7%). Two hundred and forty-four infections (50.5%) were community-acquired and the remaining 239 hospital-acquired infections occurred in 8% of patients admitted. The cost of treating nosocomial sepsis was 4453 pounds (48% of the antibiotic expenditure for treatment). The average cost of treatment per patient varied considerably between hospital specialties; one-third of therapeutic antibiotic expenditure was consumed by haematological patients. Thirty-one antimicrobials alone or in 45 different combinations were issued; ampicillins were the most frequently prescribed antibiotics (31%), followed by co-trimoxazole (14%) and trimethoprim (8%). The patterns of antibiotic usage are discussed and inappropriate prescriptions examined.

Antibiotic costs and prescribing patterns in a recently commissioned Liverpool teaching hospital. Part II: Antimicrobial chemoprophylaxis.

All antibiotics prescribed for prophylaxis in a major teaching hospital were prospectively surveyed during 31 consecutive days. Of 2350 patients admitted during that period, 238 (10.1%) received antibiotics for prophylaxis. A total of 1238 operations were performed during the period of study, of which 201 (16.2%) were covered with antibiotics, at a cost of 3472 pounds. The use of prophylaxis increased according to the risk of peri-operative wound contamination, from 15.8% in Class I to 52.4% in Class III operations. The average cost of chemoprophylaxis also increased correspondingly. A further 40 regimens were issued for non-surgical prophylaxis at a cost of 258 pounds. Twenty antibiotics were prescribed either alone or in 37 different combinations for surgical prophylaxis, the most frequent being cephradine (22%), metronidazole (17%), penicillin (12%), and tobramycin (11%). The mean duration of antibiotic administration for all surgical procedures was 6.1 days.