Head Injury, from Men to Model

In well developed countries, injury is the leading cause of death and disability among young adults. In less developed countries the incidence of injury is high and rapidly increasing, but the relative mortality due to injuries is overshadowed by other causes, such as infections and malnutrition. In the United States of America each year approximately 1.000.000 people are treated and released from hospital emergency departments because of head injury. About 80% of patients receiving medical attention can be categorised as mild (Glasgow Coma Score = GCS 14-15), 10% as moderate (GCS 9-13), and 10% as severe (GCS 3-8). According to the Centre of Disease Control in 1996 95 patients per 100.000 inhabitants required hospitalisation, or died because of head injury. Leading causes of traumatic brain injury (TBI) in the USA are violence (self inflicted and assault, 44% fire arms), vehicle crashes (34%), falls (9%), and other miscellaneous causes (14%). In Europe the majority of external causes of traumatic brain injury is related to road traffic accidents and accidental falls

Coronary side-effect potential of current and prospective antimigraine drugs

BACKGROUND: The antimigraine drugs ergotamine and sumatriptan may cause angina-like symptoms, possibly resulting from coronary artery constriction. We compared the coronary vasoconstrictor potential of a number of current and prospective antimigraine drugs (ergotamine, dihydroergotamine, methysergide and its metabolite methylergometrine, sumatriptan, naratriptan, zolmitriptan, rizatriptan, avitriptan). METHODS AND RESULTS: Concentration-response curves to the antimigraine drugs were constructed in human isolated coronary artery segments to obtain the maximum contractile response (Emax) and the concentration eliciting 50% of Emax (EC50). The EC50 values were related to maximum plasma concentrations (Cmax) reported in patients, obtaining Cmax/EC50 ratios as an index of coronary vasoconstriction occurring in the clinical setting. Furthermore, we studied the duration of contractile responses after washout of the acutely acting antimigraine drugs to assess their disappearance from the recept

Ab initio calculation of resonant X-ray scattering in Manganites

We study the origin of the resonant x-ray signal in manganites and generalize the resonant cross-section to the band structure framework. With {\it ab initio} LSDA and LSDA+U calculations we determine the resonant x-ray spectrum of LaMnO$_3$. The calculated spectrum and azimuthal angle dependence at the Mn $K$-edge reproduce the measured data without adjustable parameters. The intensity of this signal is directly related to the orthorhombicity of the lattice. We also predict a resonant x-ray signal at the La $L$-edge, caused by the tilting of the MnO$_6$ octahedra. This shows that the resonant x-ray signal in the hard x-ray regime can be understood in terms of the band structure of a material and is sensitive to the fine details of crystal structure.Comment: 4 pages, 4 figures, accepted for publication in Phys. Rev.

Investigations with GMC2021 in experimental models predictive of antimigraine activity and coronary side-effect potential

Abstract Several acutely acting antimigraine drugs, including sumatriptan and other second generation 5-HT1D receptor agonists, have the ability to constrict porcine carotid arteriovenous anastomoses as well as the human isolated coronary artery. These two experimental models seem to serve as indicators, respectively, for the therapeutic and coronary side-effect potential of the compounds. Using these two models, we have now investigated the effects of GMC2021 (3-[2-(dimethylanimo)ethyl]-5-[(trifluoromethyl)sulfonyl]oxy][1 H]indole oxalate, a close analogue of sumatriptan. GMC2021 (30, 100, 300 and 1000 μg · kg−1, i.v.) decreased the total carotid blood flow by exclusively decreasing arteriovenous anastomotic blood flow; capillary blood flow to the skin and ears was moderately increased. The mean ± S.E.M. dose of GMC2021 eliciting a 50% decrease (ED50) in the porcine carotid arteriovenous anastomotic blood flow was found to be 1.1 ± 0.3 μmol · kg−1 and the highest dose (1000 μg · kg−1) produced a 67 ± 4% reduction. The carotid haemodynamic effects of GMC2021 were reduced by the selective 5-HT1D receptor antagonist, GR127935 (N-[methoxy-3-(4-methyl-1-piperazinyl)phenyl]-2′-methyl-4′-(5-methyl-1,2,4-oxadiazol-3-yl)[1,1-biphenyl]-4-carbboxamide hydrochloride), which completely antagonizes porcine carotid haemodynamic responses to sumatriptan (ED50: 0.16 μmol · kg−1, i.v.). Compared to sumatriptan (pD2: 6.12 ± 0.15; Emax: 31.3 ± 12.3% of contractions to 100 mM K+), GMC2021 was less potent in constricting the human isolated coronary artery (pD2: 5.45 ± 0.2; Emax: 21.0 ± 4.8% of contractions to 100 mM K+). The above results suggest that GMC2021 constricts carotid arteriovenous anastomoses partly by a 5-HT1D receptor and partly by another, probably novel, receptor and that GMC2021 should be able to abort migraine headaches in patients, with perhaps a less propensity for coronary side effects

Effects of avitriptan, a new 5 HT(1B/1D) receptor agonist, in experimental models predictive of antimigraine activity and coronary side-effect potential

Abstract Several acutely acting antimigraine drugs, including ergotamine and sumatriptan, have the ability to constrict porcine arteriovenous anastomoses as well as the human isolated coronary artery. These two experimental models seem to serve as indicators, respectively, f

Ten technical aspects of baseplate fixation in reverse total shoulder arthroplasty for patients without glenoid bone loss: a systematic review

The aim of this systematic review was to collect evidence on the following 10 technical aspects of glenoid baseplate fixation in reverse total shoulder arthroplasty (rTSA): screw insertion angles; screw orientation; screw quantity; screw length; screw type; baseplate tilt; baseplate position; baseplate version and rotation; baseplate design; and anatomical safe zones. Five literature libraries were searched for eligible clinical, cadaver, biomechanical, virtual planning, and finite element analysis studies. Studies including patients >16 years old in which at least one of the ten abovementioned technical aspects was assessed were suitable for analysis. We excluded studies of patients with: glenoid bone loss; bony increased offset-reversed shoulder arthroplasty; rTSA with bone grafts; and augmented baseplates. Quality assessment was performed for each included study. Sixty-two studies were included, of which 41 were experimental studies (13 cadaver, 10 virtual planning, 11 biomechanical, and 7 finite element studies) and 21 were clinical studies (12 retrospective cohorts and 9 case-control studies). Overall, the quality of included studies was moderate or high. The majority of studies agreed upon the use of a divergent screw fixation pattern, fixation with four screws (to reduce micromotions), and inferior positioning in neutral or anteversion. A general consensus was not reached on the other technical aspects. Most surgical aspects of baseplate fixation can be decided without affecting fixation strength. There is not a single strategy that provides the best outcome. Therefore, guidelines should cover multiple surgical options that can achieve adequate baseplate fixation

Between-hospital variation in rates of complications and decline of patient performance after glioblastoma surgery in the dutch Quality Registry Neuro Surgery

Introduction For decisions on glioblastoma surgery, the risk of complications and decline in performance is decisive. In this study, we determine the rate of complications and performance decline after resections and biopsies in a national quality registry, their risk factors and the risk-standardized variation between institutions. Methods Data from all 3288 adults with first-time glioblastoma surgery at 13 hospitals were obtained from a prospective population-based Quality Registry Neuro Surgery in the Netherlands between 2013 and 2017. Patients were stratified by biopsies and resections. Complications were categorized as Clavien-Dindo grades II and higher. Performance decline was considered a deterioration of more than 10 Karnofsky points at 6 weeks. Risk factors were evaluated in multivariable logistic regression analysis. Patient-specific expected and observed complications and performance declines were summarized for institutions and analyzed in funnel plots. Results For 2271 resections, the overall complication rate was 20 % and 16 % declined in performance. For 1017 biopsies, the overall complication rate was 11 % and 30 % declined in performance. Patient-related characteristics were significant risk factors for complications and performance decline, i.e. higher age, lower baseline Karnofsky, higher ASA classification, and the surgical procedure. Hospital characteristics, i.e. case volume, university affiliation and biopsy percentage, were not. In three institutes the observed complication rate was significantly less than expected. In one institute significantly more performance declines were observed than expected, and in one institute significantly less. Conclusions Patient characteristics, but not case volume, were risk factors for complications and performance decline after glioblastoma surgery. After risk-standardization, hospitals varied in complications and performance declines.Scientific Assessment and Innovation in Neurosurgical Treatment Strategie

To continue or not to continue? Antipsychotic medication maintenance versus dose-reduction/discontinuation in first episode psychosis: HAMLETT, a pragmatic multicenter single-blind randomized controlled trial

BACKGROUND: Antipsychotic medication is effective for symptomatic treatment in schizophrenia-spectrum disorders. After symptom remission, continuation of antipsychotic treatment is associated with lower relapse rates and lower symptom severity compared to dose reduction/discontinuation. Therefore, most guidelines recommend continuation of treatment with antipsychotic medication for at least 1 year. Recently, however, these guidelines have been questioned as one study has shown that more patients achieved long-term functional remission in an early discontinuation condition-a finding that was not replicated in another recently published long-term study. METHODS/DESIGN: The HAMLETT (Handling Antipsychotic Medication Long-term Evaluation of Targeted Treatment) study is a multicenter pragmatic single-blind randomized controlled trial in two parallel conditions (1:1) investigating the effects of continuation versus dose-reduction/discontinuation of antipsychotic medication after remission of a first episode of psychosis (FEP) on personal and social functioning, psychotic symptom severity, and health-related quality of life. In total 512 participants will be included, aged between 16 and 60 years, in symptomatic remission from a FEP for 3-6 months, and for whom psychosis was not associated with severe or life-threatening self-harm or violence. Recruitment will take place at 24 Dutch sites. Patients are randomized (1:1) to: continuation of antipsychotic medication until at least 1 year after remission (original dose allowing a maximum reduction of 25%, or another antipsychotic drug in similar dose range); or gradual dose reduction till eventual discontinuation of antipsychotics according to a tapering schedule. If signs of relapse occur in this arm, medication dose can be increased again. Measurements are conducted at baseline, at 3, and 6 months post-baseline, and yearly during a follow-up period of 4 years. DISCUSSION: The HAMLETT study will offer evidence to guide patients and clinicians regarding questions concerning optimal treatment duration and when to taper off medication after remission of a FEP. Moreover, it may provide patient characteristics associated with safe dose reduction with a minimal risk of relapse. TRIAL STATUS: Protocol version 1.3, October 2018. The study is active and currently recruiting patients (since September 2017), with the first 200 participants by the end of 2019. We anticipate completing recruitment in 2022 and final assessments (including follow-up 3.5 years after phase one) in 2026. TRIAL REGISTRATION: European Clinical Trials Database, EudraCT number 2017-002406-12. Registered 7 J