Patient-reported outcome measures in patients with familial cerebral cavernous malformations: results from the Treat_CCM trial

BackgroundThe Phase 1/2 Treat_CCM randomized controlled trial for people with familial cerebral cavernous malformations (FCCMs) confirmed the safety of propranolol and suggested beneficial effects on intracerebral hemorrhage or new focal neurological deficits, but the effects on patient-reported outcome measures have not been reported.MethodsParticipants completed self-reported questionnaires at baseline, 1 and 2 years. Depression was assessed with the Beck Depression Inventory-II (BDI-2); Anxiety with the State–Trait Anxiety Inventory X1 and X2 (STAI X-1 and STAI X-2); and Quality of Life with the Short Form 36 (SF-36), split into the physical and mental component scales (PCS and MCS). Differences between treatment groups and the general population were assessed. Change over time by treatment was assessed by means of mixed models.ResultsIn total, 71 participants (48 propranolol and 23 standard care) were enrolled, of whom 61 (73%) completed questionnaires at baseline and 2-year FU. At baseline, no differences between treatment groups for any of the questionnaires were present. Twenty (31.7%) patients were considered depressed at baseline, while this proportion was lower in the propranolol group after 2 years (28.6% vs. 55.5%, p = 0.047). The STAI X-1 and X-2 scores were stable over time. PCS was lower in FCCM patients as compared with the general Italian population, while the MCS was similar to the general population. No effect of propranolol was found for both PCS and MCS.ConclusionDepression is common among patients with FCCM. Patients randomized to propranolol had a lower proportion of participants with depression after 2 years.Clinical trial registration: https://clinicaltrials.gov/, identifier (NCT03589014)

Cardiotoxicity of Freon among refrigeration services workers: comparative cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Freon includes a number of gaseous, colorless chlorofluorocarbons. Although freon is generally considered to be a fluorocarbon of relatively low toxicity; significantly detrimental effects may occur upon over exposure. The purpose of the present study is to investigate whether occupational exposure to fluorocarbons can induce arterial hypertension, myocardial ischemia, cardiac arrhythmias, elevated levels of plasma lipids and renal dysfunction.</p> <p>Methods</p> <p>This comparative cross-sectional study was conducted at the cardiology clinic of the Suez Canal Authority Hospital (Egypt). The study included 23 apparently healthy male workers at the refrigeration services workshop who were exposed to fluorocarbons (FC 12 and FC 22) and 23 likewise apparently healthy male workers (unexposed), the control group. All the participants were interviewed using a pre-composed questionnaire and were subjected to a clinical examination and relevant laboratory investigations.</p> <p>Results</p> <p>There were no significant statistical differences between the groups studied regarding symptoms suggesting arterial hypertension and renal affection, although a significantly higher percentage of the studied refrigeration services workers had symptoms of arrhythmias. None of the workers had symptoms suggesting coronary artery disease. Clinical examination revealed that the refrigeration services workers had a significantly higher mean pulse rate compared to the controls, though no significant statistical differences were found in arterial blood pressure measurements between the two study groups. Exercise stress testing of the workers studied revealed normal heart reaction to the increased need for oxygen, while sinus tachycardia was detected in all the participants. The results of Holter monitoring revealed significant differences within subject and group regarding the number of abnormal beats detected throughout the day of monitoring (p < 0.001). There were no significant differences detected in the average heart rate during the monitoring period within subject or group. Most laboratory investigations revealed absence of significant statistical differences for lipid profile markers, serum electrolyte levels and glomerular lesion markers between the groups except for cholesterol and urinary β2-microglobulin (tubular lesion markers) levels which were significantly elevated in freon exposed workers.</p> <p>Conclusions</p> <p>Unprotected occupational exposure to chlorofluorocarbons can induce cardiotoxicity in the form of cardiac arrhythmias. The role of chlorofluorocarbons in inducing arterial hypertension and coronary artery diseases is unclear, although significantly elevated serum cholesterol and urinary β2-microglobulin levels raise a concern.</p

Introduction to the "Scoliosis" Journal Brace Technology Thematic Series: increasing existing knowledge and promoting future developments

Bracing is the main non-surgical intervention in the treatment of idiopathic scoliosis during growth, in hyperkyphosis (and Scheuermann disease) and occasionally for spondylolisthesis; it can be used in adult scoliosis, in the elderly when pathological curves lead to a forward leaning posture or in adults after traumatic injuries. Bracing can be defined as the application of external corrective forces to the trunk; rigid supports or elastic bands can be used and braces can be custom-made or prefabricated. The state of research in the field of conservative treatment is insufficient and while it can be stated that there is some evidence to support bracing, we must also acknowledge that today we do not have a common and generally accepted knowledge base, and that instead, individual expertise still prevails, giving rise to different schools of thought on brace construction and principles of correction. The only way to improve the knowledge and understanding of brace type and brace function is to establish a single and comprehensive source of information about bracing. This is what the Scoliosis Journal is going to do through the "Brace Technology" Thematic Series, where technical papers coming from the different schools will be published

Italian guidelines for primary headaches: 2012 revised version

The first edition of the Italian diagnostic and therapeutic guidelines for primary headaches in adults was published in J Headache Pain 2(Suppl. 1):105–190 (2001). Ten years later, the guideline committee of the Italian Society for the Study of Headaches (SISC) decided it was time to update therapeutic guidelines. A literature search was carried out on Medline database, and all articles on primary headache treatments in English, German, French and Italian published from February 2001 to December 2011 were taken into account. Only randomized controlled trials (RCT) and meta-analyses were analysed for each drug. If RCT were lacking, open studies and case series were also examined. According to the previous edition, four levels of recommendation were defined on the basis of levels of evidence, scientific strength of evidence and clinical effectiveness. Recommendations for symptomatic and prophylactic treatment of migraine and cluster headache were therefore revised with respect to previous 2001 guidelines and a section was dedicated to non-pharmacological treatment. This article reports a summary of the revised version published in extenso in an Italian version

Anion complexation by neutral Lewis acidic host molecules containing tin

Typescript (photocopy).A family of synthetic host molecules have been prepared, ranging in structural complexity from spiro-annelated monocycles 16 to symmetric bicycles 12 and ditopic tricycles 14. The neutral host molecules contain either two or four Lewis acidic tin atoms functionalized with sulfur or halogen substituents. The halogenated hosts 12 and 14 were restricted to binding halide ions identical to the halogen substituent due to exchange while the sulfur substituents proved more robust, and hosts 16 were treated with a variety of anions. The complexation of anions was studied in both the solution and solid state by [^119]Sn NMR spectroscopy and X-ray crystallography. Variable temperature NMR spectra for hosts 12 illustrated dynamic exchange processes wherein the guest anion migrated into and out of the cavity (complexation-decomplexation) or was in rapid equilibration between the two tin atoms. Structural isomerism in the larger bicyclic hosts 12 e,f (in-out) was also found to be temperature as well as guest concentration dependent. Line shape simulations of the spectra with a two or three site exchange model provided kinetic and thermodynamic information about the complexation phenomena. Principally, the limits of exchange were governed by the size complementarity of the hosts' cavity and the anion volume; high specificity translated into slow rates of decomplexation for hosts 12b with fluoride and 12d with chloride. Equilibrium constants were calculated from the kinetic results and the Hildebrand-Benesi method. Stoichiometries of the various complexes were determined by the method of continuous variations or by direct observation of the complex species. The formation of 1:1 (guest:host) complexes was indicative of cooperative binding by the multidentate host compounds. Two crystalline complexes (host 12b*F and 12d*Cl) were isolated and analyzed by X-ray crystallography, which showed unequivocally that the anion was encrypted by the host molecule. The structure of the symmetrical fluoride complex was a bis-hemistannate (two trigonal bipyramidal tin atoms) while the solid state structure of the chloride complex was a stannane-stannate hybrid (one tetrahedral tin and one trigonal bipyramidal tin)

Anion complexation by neutral Lewis acidic host molecules containing tin

Typescript (photocopy).A family of synthetic host molecules have been prepared, ranging in structural complexity from spiro-annelated monocycles 16 to symmetric bicycles 12 and ditopic tricycles 14. The neutral host molecules contain either two or four Lewis acidic tin atoms functionalized with sulfur or halogen substituents. The halogenated hosts 12 and 14 were restricted to binding halide ions identical to the halogen substituent due to exchange while the sulfur substituents proved more robust, and hosts 16 were treated with a variety of anions. The complexation of anions was studied in both the solution and solid state by [^119]Sn NMR spectroscopy and X-ray crystallography. Variable temperature NMR spectra for hosts 12 illustrated dynamic exchange processes wherein the guest anion migrated into and out of the cavity (complexation-decomplexation) or was in rapid equilibration between the two tin atoms. Structural isomerism in the larger bicyclic hosts 12 e,f (in-out) was also found to be temperature as well as guest concentration dependent. Line shape simulations of the spectra with a two or three site exchange model provided kinetic and thermodynamic information about the complexation phenomena. Principally, the limits of exchange were governed by the size complementarity of the hosts' cavity and the anion volume; high specificity translated into slow rates of decomplexation for hosts 12b with fluoride and 12d with chloride. Equilibrium constants were calculated from the kinetic results and the Hildebrand-Benesi method. Stoichiometries of the various complexes were determined by the method of continuous variations or by direct observation of the complex species. The formation of 1:1 (guest:host) complexes was indicative of cooperative binding by the multidentate host compounds. Two crystalline complexes (host 12b*F and 12d*Cl) were isolated and analyzed by X-ray crystallography, which showed unequivocally that the anion was encrypted by the host molecule. The structure of the symmetrical fluoride complex was a bis-hemistannate (two trigonal bipyramidal tin atoms) while the solid state structure of the chloride complex was a stannane-stannate hybrid (one tetrahedral tin and one trigonal bipyramidal tin)