A walk in the PARC: developing and implementing 21st century chemical risk assessment in Europe.

Current approaches for the assessment of environmental and human health risks due to exposure to chemical substances have served their purpose reasonably well. Nevertheless, the systems in place for different uses of chemicals are faced with various challenges, ranging from a growing number of chemicals to changes in the types of chemicals and materials produced. This has triggered global awareness of the need for a paradigm shift, which in turn has led to the publication of new concepts for chemical risk assessment and explorations of how to translate these concepts into pragmatic approaches. As a result, next-generation risk assessment (NGRA) is generally seen as the way forward. However, incorporating new scientific insights and innovative approaches into hazard and exposure assessments in such a way that regulatory needs are adequately met has appeared to be challenging. The European Partnership for the Assessment of Risks from Chemicals (PARC) has been designed to address various challenges associated with innovating chemical risk assessment. Its overall goal is to consolidate and strengthen the European research and innovation capacity for chemical risk assessment to protect human health and the environment. With around 200 participating organisations from all over Europe, including three European agencies, and a total budget of over 400 million euro, PARC is one of the largest projects of its kind. It has a duration of seven years and is coordinated by ANSES, the French Agency for Food, Environmental and Occupational Health & Safety.

Development and preliminary validation of the patient-reported Chronic Itch Burden Scale assessing health-related quality of life in chronic pruritus.

BACKGROUND: Chronic pruritus (CP) significantly affects patients' health-related quality of life (HRQoL). Very few self-reported HRQoL questionnaires exploring CP have been developed according to international guidelines, thus limiting their use in preauthorization trials. OBJECTIVES: To develop a self-reported HRQoL questionnaire in patients with CP owing to psoriasis, atopic dermatitis, seborrhoeic dermatitis of the scalp or idiopathic dermatitis, and to explore the preliminary psychometric properties of the questionnaire. METHODS: The study was performed in France. A conceptual framework was developed based on a structured literature review and expert insight, and was improved using three focus groups involving 19 participants. A 50-item questionnaire was created and tested with 21 participants using cognitive debriefings; 11 items were removed. A cross-sectional study including 251 participants was performed to explore the preliminary psychometric properties of the 39-item questionnaire. Dimensionality was explored using principal component analysis. Cronbach's alpha and correlation coefficients (interitem, item-total score and item-dimension score) were measured. The number of items was reduced through expert consensus. RESULTS: In the 39-item version, three main dimensions were identified (Cronbach's alpha = 0·94) and all correlation coefficients were > 0·34. Upon review, 13 items were deleted owing to poor quality and six items were deleted by the team, generating a 20-item version. The questionnaire's factorial structure was best reflected with a two-dimension solution, i.e. (i) social and emotional repercussions and (ii) relation to others, fear of judgement. CONCLUSIONS: The Chronic Itch Burden Scale patient-reported questionnaire explores broad aspects of HRQoL that are relevant for patients with various skin diseases. Its good cross-sectional validity makes it useful for trials and practitioners.

Tolerance and efficacy of a new celastrol-containing balm as adjunct care in psoriasis.

BACKGROUND: In patients with psoriasis, the non-lesional skin also presents abnormalities, requiring emollient application on the whole body. OBJECTIVES: To evaluate the tolerance of a new emollient balm containing celastrol, an active ingredient with anti-Th17 immunomodulatory properties used alone or in association with topical or systemic drug treatments or phototherapy, and its efficacy when used alone. METHODS: Adults with body plaque psoriasis applied the product over the whole body once a day for 4 weeks (balm used alone in 41 patients and with ongoing treatment in 50 patients). At D1, D8 ('balm alone' study) or D15 ('balm in association' study) and D29, the dermatologist rated physical and functional signs and assessed pruritus and body global lesion score (evaluating erythema, induration/thickness, scaling and dryness) in the 'balm alone' study. RESULTS: No reaction related to the product was reported, and the tolerance was deemed excellent. In the 'balm alone' study, mean pruritus intensity score significantly decreased at D8 (-39%, P < 0.001) and D29 (-60%, P < 0.001) compared with D1, together with the body global lesion score (-24% at D8 and -26% at D29, P < 0.001). In parallel, quality of life improved, as evidenced by a patient-reported outcome questionnaire. Cosmetic acceptability was good. CONCLUSION: This new emollient balm was very well tolerated by patients with body plaque psoriasis either alone or in association with drug treatment or phototherapy, which is important to ensure long-term compliance. Daily application during one month improved pruritus, physical signs and quality of life.

Beyond just the operating room: characterizing the complete caseload of a tertiary acute care surgery service.

BACKGROUND: Most studies evaluating acute care surgery (ACS) models of care for patients with emergency general surgery (EGS) conditions have focused on patients who undergo surgery while admitted under the care of the ACS service. The purpose of this study was to prospectively examine the case mix of admissions and consultations to an ACS service at a tertiary centre to identify the frequency and distribution of both operatively and nonoperatively managed EGS conditions. METHODS: In this prospective cohort study, we evaluated consecutive patients assessed by the ACS team between July 1 and Aug. 31, 2015, at a large Canadian tertiary care centre. This included all consultations and outside hospital transfers. Diagnoses, demographic characteristics, comorbidities, intervention(s), complications, readmission and in-hospital death were captured. RESULTS: The ACS team was involved in the care of 359 patients, 176 (49.0%) of whom were admitted under the direct care of the ACS team. Nonoperative care was indicated in 82 patients (46.6%) admitted to the ACS service and 151 (82.5%) of those admitted to a non-ACS service (p < 0.001). Bowel obstruction (37 patients [21.0%]) was the most common reason for admission, followed by wound/abscess (24 [13.6%), biliary disease (24 [13.6%]) and appendiceal disease (23 [13.1%]). Rates of 30-day return to the emergency department and readmission were 17.0% and 9.1%, respectively, and the in-hospital mortality rate was 1.7%. CONCLUSION: Acute care surgery teams care for a wide breadth of disease, a considerable amount of which is managed nonoperatively.

CONTEXTE: La plupart des études qui ont évalué les modèles de soins chirurgicaux aigus (SCA) chez des patients souffrant de problèmes de santé nécessitant un traitement de chirurgie générale (TCG) d'urgence ont porté sur des patients ayant subi une intervention lors de leur admission dans un service de SCA. Le but de cette étude était d'analyser de manière prospective la clientèle admise ou vue en consultation dans le service de SCA d'un centre de soins tertiaires pour connaître la fréquence et la distribution des problèmes de santé nécessitant un TCG d'urgence effectivement traités chirurgicalement ou autrement. MÉTHODES: Dans cette étude de cohorte prospective, nous avons évalué des patients consécutifs vus par l'équipe de SCA entre le 1er juillet et le 31 août 2015 dans un grand centre canadien de soins tertiaires. Cela incluait toutes les consultations et les transferts en provenance d'autres hôpitaux. Nous avons noté les diagnostics, les caractéristiques démographiques, les comorbidités, les interventions, les complications, réadmissions et les décès en cours d'hospitalisation. RÉSULTATS: L'équipe de SCA a assuré les soins de 359 patients, dont 176 (49,0 %) avaient été admis directement au service de SCA. Des soins non chirurgicaux étaient indiqués chez 82 patients (46,6 %) admis au service de SCA et chez 151 (82,5 %) patients admis dans d'autres services (p < 0,001). L'obstruction intestinale (37 patients [21,0 %]) a été la raison la plus fréquente des admissions, suivie de blessure ou d'abcès (24 patients [13,6 %), maladie biliaire (24 patients [13,6 %]) et maladie appendiculaire (23 patients [13,1 %]). Les taux de retour aux urgences et de réadmission dans les 30 jours ont été de 17,0 % et de 9,1 %, respectivement, et le taux de mortalité en cours d'hospitalisation a été de 1,7 %. CONCLUSION: Les équipes de soins chirurgicaux aigus prennent en charge un vaste éventail de pathologies, dont une part importante est gérée de manière non chirurgicale.

Efficacy of a Rhealba® Oat Extract-based emollient on chronic pruritus in elderly French outpatients.

BACKGROUND: Chronic pruritus, defined as itch persisting more than 6 weeks, is a debilitating problem that affects one in four elderly adults. Emollients are recommended for the management of pruritus, but evidence of efficacy is scarce. OBJECTIVE: Assess the efficacy of a Rhealba® Oat Extract-based emollient in the management of chronic pruritus in elderly outpatients. METHODS: This was a randomized, mono-centric, open-label, cross-over study in adults ≥60 years of age with xerosis associated with chronic pruritus. Subjects were randomized 1:1 to start with a 2-week non-treatment phase or a 2-week treatment phase in which they applied the emollient once or twice daily. The primary outcome was subject-assessed pruritus using an established visual analogue scale. Subjects also assessed pruritus using the 5-D itch scale. Investigators assessed xerosis using the Overall Dry Skin Score and measured hydration index by Corneometer® , desquamation by D-Squame and transepidermal water loss by Aquaflux® . RESULTS: Thirty subjects were included. Pruritus intensity on the visual analogue scale improved significantly more during the treatment phase than during the non-treatment phase (P < 0.0001). This was also observed immediately after the first product application (P < 0.0001). According to the 5-D itch scale, pruritus decreased during the treatment phase but remained stable during the non-treatment phase (P = 0.0042). At the end of the treatment phase, more than half of the subjects reported an improvement in pruritus, and 30% reported complete disappearance, whereas pruritus remained stable during the non-treatment phase (P < 0.0001). Xerosis improved significantly more during the treatment phase than during the non-treatment phase as measured by D-Squame, clinical assessment and hydration index (P < 0.0001). Transepidermal water loss did not significantly change. CONCLUSION: Daily use of a Rhealba Oat Extract-based emollient can provide relief to elderly adults who suffer from xerosis associated with chronic pruritus.

Distorted octahedral environments in tricarbonylrhenium(I) complexes of 5-[2-(2,4,6-trimethylphenyl)diazen-1-yl]quinolin-8-olate and 5,7-bis[2-(2-methylphenyl)diazen-1-yl]quinolin-8-olate.

The Re(I) centres of two Re(I)-tricarbonyl complexes, viz. tricarbonyl(pyridine-κN){5-[2-(2,4,6-trimethylphenyl)diazen-1-yl]quinolin-8-olato-κ(2)N(1),O}rhenium(I), [Re(C23H21N4O)(CO)3], (I), and {5,7-bis[2-(2-methylphenyl)diazen-1-yl]quinolin-8-olato-κ(2)N(1),O}tricarbonyl(pyridine-κN)rhenium(I), [Re(C28H23N6O)(CO)3], (II), are facially surrounded by three carbonyl ligands, a pyridine ligand and either a 5-[2-(2,4,6-trimethylphenyl)diazen-1-yl]quinolin-8-olate [in (I)] or a 5,7-bis[2-(2-methylphenyl)diazen-1-yl]quinolin-8-olate [in (II)] ligand, in a slightly distorted octahedral environment. The crystal structure of (I) is stabilized by two intermolecular C-H···O interactions and that of (II) is stabilized by three intermolecular C-H···O hydrogen-bonding interactions.

5-(3,4-Dimeth-oxy-benzyl-idene)-1,3-dimethyl-1,3-diazinane-2,4,6-trione.

In the title compound, C(15)H(16)N(2)O(5), the dihedral angle between 1,3-diazinane and benzene rings is only 4.27 (1)°. The essentially planar mol-ecular structure is characterized by a short intra-molecular C-H⋯O separation and by an exceptionally large bond angle of 138.25 (14)° at the bridging methine C atom. The meth-oxy groups deviate somewhat from the plane of the benzene ring, with C-C-O-C torsion angles of -15.6 (1) and 9.17 (6)°. In the crystal, mol-ecules form centrosymmetric dimers via donor-acceptor π-π inter-actions, with a centroid-centroid distance of 3.401 (1) Å.

[Bis(pyridin-2-ylmeth-yl)amine-κ(3)N,N',N'']tricarbonyl-rhenium(I) bromide hemihydrate.

The title compound, fac-[Re(C(12)H(12)N(3))(CO)(3)]Br·0.5H(2)O, crystallizes with a cationic rhenium(I) unit, a bromide ion and half a water mol-ecule, situated on a twofold rotation axis, in the asymmetric unit. The Re(I) atom is facially surrounded by three carbonyl ligands and a tridentate bis-(pyridin-2-ylmeth-yl)amine ligand in a distorted octahedral environment. N-H⋯Br, O-H⋯Br, C-H⋯O and C-H⋯Br hydrogen bonds are present in the crystal structure and π-π stacking is also observed [centroid-centroid distances = 3.669 (1) Šand 4.054 (1) Å], giving rise to a three-dimentional network. The mol-ecules pack in a head-to-head fashion along the ac plane.

N,N'-(4,5-Dimethyl-1,2-phenyl-ene)bis-(pyridine-2-carboxamide).

In the title compound, C(20)H(18)N(4)O(2), the dihedral angles between the central benzene ring and the pyridine rings are 57.55 (6) and 22.05 (8)°. The mol-ecular conformation is stabilized by intra-molecular N-H⋯N inter-actions and in the crystal structure an inter-molecular asymmetric cyclic hydrogen-bonding association involving both amide N-H donors and a common amide O-atom acceptor gives a chain extending along the c axis.

Acetonitrile-trichloridobis(cyclo-hexyl-diphenyl-phosphane)rhodium(III) acetonitrile disolvate.

In the title compound, [RhCl(3)(CH(3)CN)(C(18)H(21)P)(2)]·2CH(3)CN, the complex mol-ecule lies on a twofold rotation axis that passes through the Rh(III) atom, one Cl atom, and the C and N atoms of the coordinated acetonitrile mol-ecule. The Rh(III) atom is coordinated by two P atoms in trans positions, three Cl atoms and an acetonitrile mol-ecule in a distorted octa-hedral geometry. Intra-molecular C-H⋯Cl inter-actions are observed. The uncoordinated acetonitrile mol-ecule is disordered over two sites with occupancies of 0.588 (4) and 0.412 (4).

4,5-Bis(2,4-di-tert-butyl-phen-oxy)phthalonitrile.

In the title compound, C(36)H(44)N(2)O(2), the dihedral angles between the phthalonitrile ring and the two di-tert-butyl-benzene rings are 68.134 (8) and 70.637 (11)°. The two nitrile groups are almost coplanar with the phthalonitrile ring except for one of the N atoms which deviates from the plane by 0.125 (4) Å. One of the tert-butyl groups is disordered over two orientations, with refined occupancies of 0.814 (6) and 0.186 (6). Intra-molecular C-H⋯O inter-actions stabilize the molecular structure. The crystal packing is stabilized by inter-molecular C-H⋯N inter-actions.

Racemic tricarbon-yl[7-meth-oxy-2-(η-phen-yl)chromane]-chromium(0).

In the title compound, [Cr(C(16)H(16)O(2))(CO)(3)], the Cr(0) atom of the Cr(CO)(3) unit is coordinated to the phenyl ring of the flavan ligand in an η(6) mode, with a normal arene-to-metal distance. The Cr(CO)(3) unit exhibits a three-legged piano-stool conformation, while the dihydro-pyran ring displays a distorted envelope configuration. The phenyl ring is twisted away from the fused ring system by 25.5 (2)°. The meth-oxy group is almost coplanar with the phenyl ring [C(Me)-O-C(ar)-C(ar) torsion angle = 8.46 (2)°]. The crystal packing is stabilized by inter-molecular C-H⋯O inter-actions.

(2-Methyl-4-oxo-4H-pyran-3-olato-κO,O)bis-(triphenyl-phosphane-κP)copper(I)-triphenyl-phosphane-methanol (1/1/1).

In the title compound, [Cu(C(6)H(5)O(3))(C(18)H(15)P)(2)]·C(18)H(15)P·CH(3)OH, the pyran-4-one ring is appromimately planar (r.m.s deviation = 0.0138 Å), with the Cu(I) atom 0.451 (5) Šout of the plane. The Cu(I) atom has a distorted tetra-hedral coordination. The O-Cu-O angle is 80.07 (8)° and the P-Cu-P angle is 123.49 (3)°. The crystal packing is stablized by intra-molecular C-H⋯O inter-actions and inter-molecular C-H⋯O and O-H⋯O inter-actions.

cyclo-Tetra-µ-oxido-tetra-kis-[(acetyl-acetonato-κO,O')bis-(ethano-lato-κO)niobium(V)].

The asymmetric unit of the title tetra-nuclear niobium(V) compound, [Nb(4)(C(2)H(5)O)(8)(C(5)H(7)O(2))(4)O(4)], contains two Nb(V) atoms, two bridging O atoms, two acetyl-acetonate and four ethano-late ligands. Each Nb(V) atom is six-coordinated by the bridging O atoms, two ethano-late and one chelating acetyl-acetonate ligands. The Nb-O distances vary between 1.817 (2) and 2.201 (2) Šand the O-Nb-O angles vary between 78.88 (8) and 102.78 (9)°, illustrating the significant distortion from ideal ocahedral geometry. The rest of the tetra-nuclear unit is generated through an inversion centre. The C atoms of two of the ethano-late mol-ecules are disordered over two sites [occupancy ratio 0.601 (12):0.399 (12)].

1,1,1,5,5,5-Hexafluoro-2,4-dimeth-oxy-pentane-2,4-diol.

The title compound, C(7)H(10)F(6)O(4), was isolated as an unexpected product from a reaction of tantalum(V) methoxide with hexa-fluoro-acetyl-acetone in a methanol solution. The asymmetric unit consists of one half-mol-ecule with the middle C atom lying on a twofold axis. The crystal structure is stabilized by O-H⋯O and an array of C-H⋯F hydrogen-bonding inter-actions. These inter-actions link the mol-ecules into a stable supra-molecular three-dimensional network. The mol-ecules pack in a ribbon-like form in the ac plane as a result of these inter-actions.

Dimethyl 2,6-dimethyl-4-phenyl-pyridine-3,5-dicarboxyl-ate.

In the title compound, C(17)H(17)NO(4), the dihedral angle between the benzene and pyridine rings is 75.51 (4)°. The benzene and pyridine rings are both approximately planar (r.m.s. deviations of 0.0040 and 0.0083 Å, respectively), indicating that the pyridine N atom is not protonated. The crystal structure is stabilized by weak inter-molecular C-H⋯O and C-H⋯N inter-actions.

Bis[2-(methyl-amino)-troponato]copper(II).

In the title compound, [Cu(C(8)H(8)NO)(2)], a strictly square-planar geometry about the Cu(II) metal atom is observed. Substitution of an O atom with a methyl-functionalized N atom does not significantly alter the bond distances and angles in the copper(II) complex when compared with a similar bis-(troponato)copper(II) complex. π-π stacking is observed between the tropolone rings, with inter-planar distances of 3.5039 (16) and 3.2933 (15) Å, respectively. Additional stabilisation of the structure is accomplished through C-H⋯O hydrogen-bonding interactions.

2',3,4,4'-Tetra-meth-oxy-chalcone.

IN THE TITLE COMPOUND [SYSTEMATIC NAME: 1-(2,4-dimethoxyphenyl)-3-(3,4-dimethoxyphenyl)prop-2-en-1-one], C(19)H(20)O(5), the dihedral angle between the benzene rings is 26.88 (5)°. One of the meth-oxy groups is twisted slightly away from the plane [C-O-C-C torsion angle = -12.8 (3)°] while the others are almost co-planer [C-O-C-C torsion angles = -3.2 (3), 2.6 (3) and -3.6 (3)°]. The crystal packing is stabilized by inter-molecular C-H⋯O inter-actions. A weak intra-molecular C-H⋯O inter-action occurs.

2',3,4,4',5-Penta-meth-oxy-chalcone.

In the title chalcone [systemetic name 1-(2,4-dimeth-oxy-phen-yl)-3-(3,4,5-trimeth-oxy-phen-yl)prop-2-en-1-one], C(20)H(22)O(6), the dihedral angle between the plane of the two benzene rings is 7.03 (4)° with all but one of the meth-oxy groups essentially co-planar with these rings [C-C-O-C torsion angles = -76.1 (2), -0.7 (3), 1.8 (3), -6.2 (3), 2.0 (3)°]. An intra-molecular C-H⋯O inter-action occurs. The crystal packing is stabilized by weak inter-molecular C-H⋯O hydrogen bonds.