The selection and reporting of core outcome measures in clinical trials is essential for patients, researchers, and healthcare providers for clinical research to have an impact on healthcare. In this ...systematic scoping review, we aimed to quantify the extent to which gout clinical trials are collecting and reporting data in accordance with the core outcome domains from Outcome Measures in Rheumatology (OMERACT) published in 2009 applicable for both acute and chronic trials and evaluate the reporting according to the core domains before and after the 2009 OMERACT endorsement.
We searched multiple databases PubMed, EMBASE, the Cochrane Library including the Cochrane Central Register of Controlled Trials (CENTRAL), and Cochrane Database of Systematic Reviews (CDSR) and www.clinicaltrials.gov for randomized controlled trials (RCTs) allocating people with gout versus an active pharmacological gout treatment or a control comparator (no date limitation). We extracted the data in accordance with the core outcome sets, focusing individually on core outcome domains and the core outcome measurements for acute and chronic trials, respectively. In this study ‘Acute trials’ reflect studies that describe interventions for short term management of gout flares, and ‘chronic trials’ describe interventions for long-term urate lowering therapy in the management of gout.
From 8,522 records identified in the database search, 134 full text papers were reviewed, and 71 trials were included, of which 36 were acute and 35 were chronic. Only 3 of 36 (8%) acute trials reported all five core domains and none of the 35 included chronic trials reported all 7 core domains. In the acute trials, twenty-seven unique measurement instruments across the 5 core domains were identified. For chronic trials there were 31 unique measurement instruments used across the 7 core domains. Serum urate was reported in 100% of the chronic trials and gout flares in 80%. However, other core domains were reported in <30% of chronic trials. In particular the patient-important domains such as HR-QOL, patient global assessment and activity limitations were rarely reported. A broad variety of different measurement instruments were used to assess each endorsed core domain, a minority of trials used the OMERACT endorsed instruments. For acute trials, the number reporting on all core domains was consistently low and no change was detected before and after the endorsement of the core domains in 2009. None of the included chronic trials reported on all 7 endorsed core domains at any time.
In this study we found a low adherence with the intended endorsed (i.e., core) outcome domains for acute and chronic gout studies which represents a poor uptake of the global OMERACT efforts for the minimum of what should be measured in clinical trials. In addition, there is a significant variation in how the OMERACT endorsed outcome domains have been measured. This systematic review demonstrates the need for continuous encouragement among gout researchers to adhere to OMERACT core domains as well as further guidance on outcome measurements reporting.
Prospero: CRD42019151316
Electrical stimulation of the infraorbital nerve was used to examine the coupling between neuronal activity and cerebral blood
flow (CBF) in rat somatosensory cortex by laser Doppler flowmetry and ...extracellular recordings of field potentials.
The relationship between field potential (FP) and CBF amplitudes was examined as a function of the stimulus intensity (0â2.0
mA) at fixed frequency (3 Hz). FP amplitudes up to 2.0â2.5 mV were unaccompanied by increases of CBF. Above this threshold,
CBF and FP amplitudes increased proportionally.
At fixed stimulus intensity of 1.5 mA, CBF increases were highly correlated to FP amplitudes at low frequencies of stimulation
(< 2 Hz), but uncoupling was observed at stimulation frequencies of 2â5 Hz. The evoked responses were independent of stimulus
duration (8â32 s).
The first rise in CBF occurred within the first 0.2 s after onset of stimulation in the upper 0â250 μm of the cortex. Latencies
were longer (1.0â1.2 s) in lower cortical layers in which CBF and FP amplitudes were larger.
Local AMPA receptor blockade attenuated CBF and FP amplitudes proportionally.
This study showed that activity-dependent increases in neuronal activity and CBF were linearly coupled under defined conditions,
but neuronal activity was well developed before CBF started to increase. Consequently, the absence of a rise in CBF does not
exclude the presence of significant neuronal activity. The CBF increase in upper cortical layers preceded the rise in lower
layers suggesting that vessels close to or at the brain surface are the first to react to neuronal activity. The activity-dependent
rise in CBF was explained by postsynaptic activity in glutamatergic neurons.
Scanning laser-Doppler flowmetry (SLDF) generates two-dimensional images of blood flow. This study compared SLDF to conventional laser-Doppler flowmetry (LDF) in the cerebral circulation. Test ...stimuli were episodes of cortical spreading depression (CSD) elicited in brains of halothane anaesthetised rats (n = 9). The LDF instrument used two wavelengths of laser light to record relative changes of cerebral blood flow (CBF) up to an approximate depth of 250 microm (543 nm) and 500 microm (780 nm). Under resting conditions, SLDF images showed a heterogeneous pattern of flow in pial vessels with high flow rates in arterioles, and lower rates in venules and small vessels (<30 microm). Arterioles constituted about 6%, venules 12% and small vessels 2% of the image area, while approximately 80% were background with a laser-Doppler signal corresponding to zero calibration. During CSD, the relative increase of area was largest for small vessels and less for venules and arterioles. Similar changes were observed for blood flow in the three vessel structures. For both wavelengths of LDF, flow changes correlated with SLDF (r approximately 0.7). In conclusion, SLDF provides images of flow in pial vessels and capillaries at, or just beneath the cortical surface. SLDF and LDF are complementary, but cannot substitute for one another as they measure flow in different layers of the cortex.
Previous studies have shown that repeated injections of acidic saline, given into the lateral gastrocnemius muscle of rats, results in a bilateral reduction in withdrawal threshold to tactile ...stimulation of the hindpaws. We have now characterised this model of muscoskeletal pain pharmacologically, by evaluating the antinociceptive effects of various analgesics after systemic administration. The μ-opioid receptor agonist morphine (3 and 6 mg/kg) produced a particularly prolonged antiallodynic effect. The glutamate receptor antagonists (8-methyl-5-(4-(
N,
N-dimethylsulfamoyl)phenyl)-6,7,8,9,-tetrahydro-1H-pyrrolo3,2-
h-iso-quinoline-2,3-dione-3-
O-(4-hydroxybutyric acid-2-yl)oxime NS1209 and ketamine (6 and 15 mg/kg, respectively), the KCNQ K
+ channel openers retigabine and flupirtine (10 and 20 mg/kg, respectively) and the Na
+ channel blocker mexiletine (37.5 mg/kg) also significantly increased paw withdrawal threshold, although to a lesser degree than morphine. In contrast, the anticonvulsant lamotrigine (30 mg/kg), the cyclooxygenase-2 inhibitor carprofen (15 mg/kg) and the benzodiazepine diazepam (3 mg/kg) were ineffective. All antinociceptive effects were observed at nonataxic doses as determined by the rotarod test. These results suggest that in this model, muscle-mediated pain can be alleviated by various analgesics with differing mechanisms of action, and that once established ongoing inflammation does not appear to contribute to this process.
Objectives. Young individuals surviving severe traumatic brain injury (TBI) frequently experience a wide range of cognitive, emotional and behavioural consequences. This cross-sectional follow-up ...study investigated psychological outcome of young survivors in the chronic phase, and whether psychological outcome was associated with improvement of functional abilities during sub-acute admission.
Methods. Patients, who acquired a severe TBI during adolescence or early adulthood (n = 36) and received early intensive rehabilitation, were contacted for follow-up assessment concerning psychological outcome and completed the Adult Self Report 18-59 (ASR18-59). Demographic data, functional outcomes and severity measures were obtained from the local database.
Results. The participants had a mean age of 24.1 years (SD = 4.1) at follow-up, and the mean time since injury was 72.1 months (SD = 44.2). Results showed significantly higher scores compared with the normative reference population in relation to the subscales withdrawal/isolation (p = 0.013), attention problems (p = 0.008) and intrusive behaviour (p = 0.046). Pearson correlation analyses showed that young survivors experiencing more functional improvement during inpatient rehabilitation had fewer psychological problems during the chronic phase in the subscales: withdrawal/isolation, rule breaking, intrusive behaviour and total problems.
Conclusion. Young patients reported psychological problems in several areas during the chronic phase of injury, which may hinder complete reintegration and participation in society. Larger functional improvement during sub-acute rehabilitation seemed to be associated with less psychological problems in the chronic phase.
The sterically crowded 2,2,4,4‐tetramethyl‐3‐thioxocyclobutanone (7) and its dithio analogue 9 were found to react readily with gaseous chlorine to afford 1:1 and 1:2 adducts, respectively. The ...stable, crystalline products were identified as the α‐chlorosulfenyl chlorides 8 and 12 which yielded corresponding disulfides after treatment with equimolar amounts of thioacetic acid.
Unlike vicinal disulfenyl dichlorides whose carbon monosulfide diinsertion products readily cyclize with loss of thiophosgene, geminal disulfenyl dichlorides diinsert carbon monosulfide to form ...stable gem-bis(chlorodithioformates).
The chemistry of geminal disulfenyl dichlorides R
1
R
2
C(SCl)
2
is reviewed based on CAS and Beilstein Online substructure and supplementary searches.
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