Consensus statement from the international consensus meeting on post-traumatic cranioplasty.

BACKGROUND: Due to the lack of high-quality evidence which has hindered the development of evidence-based guidelines, there is a need to provide general guidance on cranioplasty (CP) following traumatic brain injury (TBI), as well as identify areas of ongoing uncertainty via a consensus-based approach. METHODS: The international consensus meeting on post-traumatic CP was held during the International Conference on Recent Advances in Neurotraumatology (ICRAN), in Naples, Italy, in June 2018. This meeting was endorsed by the Neurotrauma Committee of the World Federation of Neurosurgical Societies (WFNS), the NIHR Global Health Research Group on Neurotrauma, and several other neurotrauma organizations. Discussions and voting were organized around 5 pre-specified themes: (1) indications and technique, (2) materials, (3) timing, (4) hydrocephalus, and (5) paediatric CP. RESULTS: The participants discussed published evidence on each topic and proposed consensus statements, which were subject to ratification using anonymous real-time voting. Statements required an agreement threshold of more than 70% for inclusion in the final recommendations. CONCLUSIONS: This document is the first set of practical consensus-based clinical recommendations on post-traumatic CP, focusing on timing, materials, complications, and surgical procedures. Future research directions are also presented.

Presenting symptoms of glioma in adults.

OBJECTIVE: Studies on the presenting symptoms of glioma in adults in the age of readily available MRI imaging are scarce. This study investigates presenting symptoms of glioma and assesses the correlations of the presenting symptoms with patient age and histopathological class of the tumor. MATERIALS AND METHODS: A retrospective review of the medical records of histologically verified glioma patients treated in Turku University Hospital, during 2006-2010, was conducted. The associations between the presenting symptoms and other covariates were assessed individually. RESULTS: One hundred and fifty patients were ascertained. The most common presenting symptoms of glioma were seizure and cognitive disorder. Patients presenting with seizures were younger than patients with cognitive disorders, and the grade of the tumor was also found to significantly correlate with the most common presenting symptoms. Age group and tumor grade were statistically significant factors of cognitive disorder (P = 0.0037 and P = 0.0069) and age group of seizure (P = 0.0065). The associations between the presenting symptoms and the anatomical location, spread into adjacent brain areas, or laterality of the tumor or site of diagnosis were found to be statistically insignificant. Headache was not a common presenting symptom in glioma patients. CONCLUSIONS: The main presenting symptoms of glioma in adults in the MRI age still are seizures and cognitive disorder. Patient age and tumor grade correlate positively with the incidence of cognitive disorder and patient age negatively with incidence of seizure as a presenting symptom. Headache is an uncommon manifestation and does not appear as a sole symptom.

Effects of nitric oxide synthase inhibition on dexmedetomidine-induced vasoconstriction in healthy human volunteers.

BACKGROUND: This study aimed to assess the contribution of endothelial nitric oxide synthesis to the net responses of human peripheral blood vessels in vivo to the selective alpha(2)-adrenoceptor agonist dexmedetomidine. METHODS: Two groups of healthy young men were studied. In the first experiment, after brachial plexus block, the responses of digital arteries to systemically administered dexmedetomidine (target plasma concentration 1.2 ng ml(-1)) were studied using a photoplethysmograph (n=10) during i.a. infusions of saline and the nitric oxide synthase (NOS) inhibitor N(G)-monomethyl-L-arginine (L-NMMA) (8 micromol min(-1)). In a separate experiment, after pre-treatment with acetylsalicylic acid, responses to increasing doses of dexmedetomidine (0.01-164 ng min(-1)) in the presence and absence of L-NMMA were compared in dorsal hand veins (DHV) (n=10) using linear variable differential transformers. RESULTS: L-NMMA significantly augmented dexmedetomidine-induced vasoconstriction of digital arteries as assessed by an increase in light transmission through a finger and by a decrease in finger temperature. The mean (95% confidence interval) extent of the additional effect of L-NMMA over the constrictor effect of dexmedetomidine alone was 19% (14-24) (P<0.0001). In DHV, L-NMMA had variable effects on the dexmedetomidine-constriction dose-response curve. In three subjects, the curve was shifted significantly to the left (with a >10-fold difference in ED(50)), but ED(50) was only marginally affected by L-NMMA in the other subjects (difference in ED(50)

Assessing the depth of dexmedetomidine-induced sedation with electroencephalogram (EEG)-based spectral entropy.

BACKGROUND: Adequate sedation of critically ill patients improves the outcome of intensive care. Maintaining an optimal level of sedation in the intensive care unit (ICU) is difficult because of a lack of appropriate monitoring methods to guide drug dosing. Dexmedetomidine, a selective alpha(2)-adrenoceptor agonist, has recently been introduced for the sedation of ICU patients. This study investigated the utility of electroencephalogram (EEG)-based spectral entropy monitoring (with M-ENTROPY, GE Healthcare, Helsinki, Finland) for the assessment of dexmedetomidine-induced sedation. METHODS: Eleven healthy, non-smoking men, aged 23.9 +/- 2.5 years (mean +/- standard deviation), were recruited. Spectral entropy was recorded before and during low (0.5 ng/ml) and high (5 ng/ml) plasma concentrations of dexmedetomidine. At the end of the infusion, subjects were awakened by verbal command and light shaking. RESULTS: Spectral entropy decreased from 84 +/- 5 to 66 +/- 16 (P= 0.029) during low dexmedetomidine levels and from 84 +/- 5 to 20 +/- 12 (P < 0.001) during high dexmedetomidine levels. Transitions during loss and regaining of consciousness were analysed separately. Entropy decreased from 76 +/- 8 before to 43 +/- 10 (P < 0.001) after loss of consciousness, and increased from 14 +/- 4 to 63 +/- 13 (P < 0.001) on regaining of consciousness. These changes were consistent across all subjects. Prediction probability and sensitivity values indicated a high predictive performance of the method. CONCLUSION: The depth of dexmedetomidine-induced sedation can be monitored with EEG-based spectral entropy. These results should be confirmed in a clinical setting.

Dissolution rate limited bioavailability of flutamide, and in vitro - in vivo correlation.

Flutamide is due to its properties as a practically water-insoluble, high-dose drug substance a typical representative of a drug with particle size limited dissolution rate and bioavailability. An in vitro dissolution test method comprising of standard paddle stirrer, round-bottomed vessel of 4 l capacity, and 0.1 N hydrochloric acid with 0.5% of sodium lauryl sulphate as dissolution medium, was developed. The dissolution method was shown discriminatory and predictive regarding bioavailability of conventional 250 mg flutamide tablets with different in vitro dissolution rates. Relative bioavailability of flutamide from the tablets, determined as AUC of the active metabolite 2-hydroxyflutamide in healthy male subjects, could be correlated with drug amount dissolved during 45 min in the in vitro test. Also bioavailability data from four different biostudies could be compared utilising the calculated ratios R(AUC) and R(Diss.) for the test and reference formulations in the individual studies. It is suggested that the concept of R(AUC) and R(Diss.) can also be applied to other orally administered, poorly soluble, high-dose drug substances with dissolution rate limited bioavailability.

Treatment of xerostomia through use of dentures containing reservoirs of saliva substitute.

A 53-year-old woman was referred to the University Dental Clinic because of ocular and oral dryness during the previous year. She also had urticaria and was receiving medication for postmenopausal hormonal problems. The patient was wearing full dentures. Resting saliva flow rate (RSFR) and stimulated saliva flow rate (SSFR) were 0 ml/5 minutes and 0.5 ml/10 minutes, respectively. The patient was given Sulfarlem (trithioparamethoxyphenylpropene), tablets (25 mg) for six months. There was no significant improvement in flow rate. Medication was terminated as ineffective. Seven months later, full dentures with reservoirs of saliva substitute were constructed according to Vissink. The reservoir of the upper denture functioned satisfactorily for two weeks, after which the latex membrane valve became detached. The valve system was replaced with a Gerber matrix housing, which functions even without a latex membrane. The dentures were further improved by making a stainless steel plug constructed from a burr fitting into the matrix housing. This was found to effective in reducing the discharge of saliva substitute from the reservoir. Symptomatic treatment may be the treatment of choice in cases of xerostomia where no functional salivary gland tissue is present.

Bioavailability of paediatric mixtures containing phenoxymethylpenicillin calcium or potassium salt.

The bioavailability of the calcium and potassium salts of phenoxymethyl-penicillin (dose 38,000 I.U./kg) was investigated in eight healthy adult volunteers. Administration of the calcium salt as an aqueous oral mixture resulted in a mean peak plasma concentration of 8.52 mg/l (SD 1 X 96) and that of the potassium salt mixture in a concentration of 8.40 mg/ml (SD 2.61), p greater than 0.1. The median time-to-peak levels were 0.75 h and 1.0 h, respectively (p greater than 0.1). The mean AUC for the calcium salt mixture was 16.94 mg X h/l (SD 3.31) and for the potassium salt 15.84 mg X h/l (SD 4.76), p less than 0.09. These findings confirm that an aqueous mixture of calcium phenoxymethylpenicillin is equivalent to a mixture of potassium phenoxymethylpenicillin.