Impact of a clinical pharmacist's intervention on pneumococcal vaccination in a population of at- risk hospitalized patients: The IP-VAC study.

OBJECTIVES: The aim of this study was to evaluate the impact of clinical pharmacist intervention on compliance with pneumococcal vaccination (PV) recommendations in hospitalized patients. METHODS: This was a prospective, single-center, before-and-after study conducted in 2019-2020. Patients had to be over 18 years of age, at risk of pneumococcal infection, and with no PV. No changes were made in the observational phase. During the interventional phase, the clinical pharmacist discussed a prescription for preventive PV and a mention in the discharge letter. A pharmaceutical consultation sensitized the patient to the interest of PV. The clinical pharmacist ensured that a complete vaccination protocol would be carried out by the retail pharmacist within 3 months of hospitalization. RESULTS: One hundred and sixty-seven (167) patients were included. In the observational phase, 2.3% of patients received a complete vaccination protocol after discharge from primary care. The rate increased to 63.8% after the clinical pharmacist's intervention (p < 0.001). Vaccines were prescribed by hospital physicians in 97.5% of cases, while 40% of discharge letters included the indication for PV. CONCLUSION: The clinical pharmacist's intervention led to delivery of a complete PV protocol after discharge for over half the patients. This study demonstrated the feasibility of a pharmaceutical intervention to promote PV in hospital activities.

Deciphering the natural history of SCA7 in children.

BACKGROUND AND PURPOSE: Childhood-onset autosomal dominant cerebellar ataxia type 7 (SCA7) is a severe disease which leads to premature loss of ambulation and death. Early diagnosis of SCA7 is of major importance for genetic counselling and still relies on specific genetic testing, driven by clinical expertise. However, the precise phenotype and natural history of paediatric SCA7 has not yet been fully described. Our aims were to describe the natural history of SCA7 in a large multicentric series of children of all ages, and to find correlates to variables defining this natural history. METHODS: We collected and analysed clinical data from 28 children with proven SCA7. All had clinical manifestations of SCA7 and either a definite number of CAG repeats in ATXN7 or a long expansion > 100 CAG. RESULTS: We identified four clinical presentation patterns related to age at onset. Children of all age groups had cerebellar atrophy and retinal dystrophy. Our data, combined with those in the literature, suggest that definite ranges of CAG repeats determine paediatric SCA7 subtypes. The number of CAG repeats inversely correlated to all variables of the natural history. Age at gait ataxia onset correlated accurately to age at loss of walking ability and to age at death. CONCLUSION: SCA7 in children has four presentation patterns that are roughly correlated to the number of CAG repeats. Our depiction of the natural history of SCA7 in children may help in monitoring the effect of future therapeutic trials.

MR Imaging Correlates for Molecular and Mutational Analyses in Children with Diffuse Intrinsic Pontine Glioma.

BACKGROUND AND PURPOSE: Recent advances in molecular techniques have characterized distinct subtypes of diffuse intrinsic pontine gliomas. Our aim was the identification of MR imaging correlates of these subtypes. MATERIALS AND METHODS: Initial MRIs from subjects with diffuse intrinsic pontine gliomas recruited for a prospective clinical trial before treatment were analyzed. Retrospective imaging analyses included FLAIR/T2 tumor volume, tumor volume enhancing, the presence of cyst and/or necrosis, median, mean, mode, skewness, kurtosis of ADC tumor volume based on FLAIR, and enhancement at baseline. Molecular subgroups based on EGFR and MGMT mutations were established. Histone mutations were also determined (H3F3A, HIST1H3B, HIST1H3C). Univariate Cox proportional hazards regression was used to test the association of imaging predictors with overall and progression-free survival. Wilcoxon rank sum, Kruskal-Wallis, and Fisher exact tests were used to compare imaging measures among groups. RESULTS: Fifty patients had biopsy and MR imaging. The median age at trial registration was 6 years (range, 3.3-17.5 years); 52% were female. On the basis of immunohistochemical results, 48 patients were assigned to 1 of 4 subgroups: 28 in MGMT-/epidermal growth factor receptor (EGFR)-, 14 in MGMT-/EGFR+, 3 in MGMT+/EGFR-, and 3 in MGMT+/EGFR+. Twenty-three patients had histone mutations in H3F3A, 8 in HIST1H3B, and 3 in HIST1H3C. Enhancing tumor volume was near-significantly different across molecular subgroups (P = .04), after accounting for the false discovery rate. Tumor volume enhancing, median, mode, skewness, and kurtosis ADC T2-FLAIR/T2 were significantly different (P ≤ .048) between patients with H3F3A and HIST1H3B/C mutations. CONCLUSIONS: MR imaging features including enhancement and ADC histogram parameters are correlated with molecular subgroups and mutations in children with diffuse intrinsic pontine gliomas.

[Risk of Infection Following Implant of Artificial Penile Nodule, Bouglous or Dominos: A Case Report in French Guiana]. / Risques d'infection suite à l'implant de nodules péniens bouglous ou dominos : à propos d'un cas en Guyane française.

Implant of artificial penile nodule (APN) is a socio-cultural practice, linked to penitentiary environment in French Guiana. Physicians are often unfamiliar with its existence. Although serious complications remain low regarding the high prevalence of this practice, urgent cares could be required. Indeed, implant of nodule can have functional sequelae, and sometimes life-threatening consequences, especially if infection occurs and spreads. We have reported the case of a 23-year-old male who presented an infection of the penis after the implant of two APN. Removal of the nodules associated with oral antibiotics was needed. We also present CT-scan images of another patient, as an example of fortuitous discovery of these nodules. We finally discuss the various complications already described in literature.

Le port de nodules péniens artificiels (NPA) est fortement lié à la fréquentation du milieu carcéral en Guyane française. Cette pratique est peu connue des professionnels de santé. Bien que les complications restent peu fréquentes malgré la prévalence élevée de ces nodules dans certaines populations, elles peuvent nécessiter une prise en charge diagnostique et thérapeutique urgente. En effet, il existe des risques fonctionnels, mais également vitaux survenant dans les suites d'une complication notamment infectieuse. Nous rapportons ici le cas d'une infection de la verge suite à l'implant de deux NPA chez un patient de 23 ans, pour laquelle le retrait des nodules et une antibiothérapie orale ont été nécessaires. Preuve de la forte prévalence de cette pratique, nous illustrons à l'aide d'une iconographie radiologique originale le cas d'un autre patient chez qui ces nodules ont été fortuitement découverts. Enfin, nous discutons des différentes complications décrites dans la littérature.

A phase Ib dose allocation study of oral administration of lucitanib given in combination with fulvestrant in patients with estrogen receptor-positive and FGFR1-amplified or non-amplified metastatic breast cancer.

PURPOSE: The primary objective of this multicentric dose allocation and dose expansion study was to determine the MTD and the DLTs of the lucitanib (a tyrosine kinase inhibitor of the FGFR/VEGFR/PDFGR pathways)/fulvestrant combination. METHODS: Postmenopausal women with ER+/HER2- mBC, who have relapsed during or after treatment with fulvestrant, were eligible. The study had a dose allocation part to assess the tolerability of the combination followed by a dose expansion part. RESULTS: Eighteen patients with ER+, mBC were enrolled; median age was 66 years, 50% had a PS: 0 and all had received previous endocrine treatment. The study was prematurely terminated after 18 patients (15 in part 1 and 3 in part 2) based on preclinical experiments that failed to confirm the hypothesis that addition of lucitanib would reverse sensitivity to endocrine treatments. Based on data of global lucitanib development, it was decided to stop the dose allocation at 12.5 mg and to start the dose expansion part at 10 mg/day. The most common grade ≥ 3 toxicities (> 10% of patients) were hypertension (78%) and asthenia (22%). All patients required at ≥ 1 interruption, 13 patients (72%) required ≥ 1 dose reduction. Three patients (72%) withdrew from the study for AEs (at 10 mg). Three patients achieved a confirmed PR (10 mg n = 1; 12.5 mg n = 2). CONCLUSION: Although the combination is feasible it requires close monitoring of the patients for the management of adverse events. Further investigation is required to better understand the potential role of FGFR inhibition in reversing resistance to endocrine treatment.

Symmetry Breaking in Photonic Crystals: On-Demand Dispersion from Flatband to Dirac Cones.

We demonstrate that symmetry breaking opens a new degree of freedom to tailor energy-momentum dispersion in photonic crystals. Using a general theoretical framework in two illustrative practical structures, we show that breaking symmetry enables an on-demand tuning of the local density of states of the same photonic band from zero (Dirac cone dispersion) to infinity (flatband dispersion), as well as any constant density over an adjustable spectral range. As a proof of concept, we demonstrate experimentally the transformation of the very same photonic band from a conventional quadratic shape to a Dirac dispersion, a flatband dispersion, and a multivalley one. This transition is achieved by finely tuning the vertical symmetry breaking of the photonic structures. Our results provide an unprecedented degree of freedom for optical dispersion engineering in planar integrated photonic devices.

Electric field effects on phase transitions in the 8CB liquid crystal doped with ferroelectric nanoparticles.

The influence of a low ac electric field on phase transitions is discussed in the case of a nematic liquid crystal 4-n-octyl-4^{'}-cyanobiphenyl (8CB) doped with Sn_{2}P_{2}S_{6} ferroelectric nanoparticles. The phase-transition temperatures obtained from temperature-dependent dielectric measurements were higher than those determined by the calorimetric method. This difference is explained by the presence of the measuring electric field which induces two effects. The first one is the amplification of the interactions between the nanoparticle polarization and the liquid-crystal order parameter. The second one is the field-induced disaggregation or aggregation process at high nanoparticle concentrations.

Compensated Arrhenius formalism applied to a conductivity study in poly(propylene glycol) diacrylate monomers.

The temperature dependence of the ionic conductivity is studied in a series of poly(propylene glycol) diacrylate monomers. The experimental data are analyzed by means of the approach recently proposed by Petrowsky et al. [J. Phys. Chem. B. 113, 5996 (2009)10.1021/jp810095g]. This so-called compensated Arrhenius formalism (CAF) approach takes into account the influence of the dielectric permittivity on the exponential prefactor in the classical Arrhenius equation. The experimental data presented in this paper show a good agreement with the CAF; this means that the exponential prefactor is principally dielectric permittivity dependent. The compensated data revealed two conduction processes with different activation energies; they correspond to low and high temperature ranges, respectively.

On the phase transitions of 8CB/Sn2P2S6 liquid crystal nanocolloids.

Using differential scanning calorimetry measurements, the influence of Sn2P2S6 ferroelectric nanoparticles on the phase transition temperatures of the 8CB liquid crystal is studied. The spontaneous polarization, ionic and anchoring effects are discussed. For low concentration of dopant, the global effect leads to a decrease and an increase of the nematic-isotropic and the smectic A-nematic phase transition temperatures, respectively. For high concentrations, due to aggregates formation, the predominant anchoring effect induces a decrease of the both phase transition temperatures.

Designs of drug-combination phase I trials in oncology: a systematic review of the literature.

BACKGROUND: Combining several anticancer agents can increase the overall antitumor action, but at the same time, it can also increase the overall observed toxicity. Adaptive dose-escalation designs for drug combinations have recently emerged as an attractive alternative to algorithm-based designs, and they seem more effective in combination recommendations. These methods are not used in practice currently. Our aim is to describe international scientific practices in the setting of phase I drug combinations in oncology. MATERIAL AND METHODS: A bibliometric study on phase I dose-finding combination trials was conducted using the Medline(®) PubMed database between 1 January, 2011, and 31 December 2013. Sorting by abstract, we selected all papers involving a minimum of two agents and then retained only those in which at least two agents were dose-escalated. RESULTS: Among the 847 references retrieved, 162 papers reported drug-combination phase I trials in which at least two agents were dose-escalated. In 88% of trials, a traditional or modified 3 + 3 dose-escalation design was used. All except one trial used a design developed for single-agent evaluation. Our study suggests that drug-combination phase I trials in oncology are very safe, as revealed by the calculated median dose-limiting toxicity rate of 6% at the recommended dose, which is far below the target rate in these trials (33%). We also examined requirements of phase I clinical trials in oncology with drug combinations and the potential advantages of novel approaches in early phases. CONCLUSION: Efforts to promote novel and innovative approaches among statisticians and clinicians appear valuable. Adaptive designs have an important role to play in early phase development.

Competing designs for drug combination in phase I dose-finding clinical trials.

The aim of phase I combination dose-finding studies in oncology is to estimate one or several maximum tolerated doses (MTDs) from a set of available dose levels of two or more agents. Combining several agents can indeed increase the overall anti-tumor action but at the same time also increase the toxicity. It is, however, unreasonable to assume the same dose-toxicity relationship for the combination as for the simple addition of each single agent because of a potential antagonist or synergistic effect. Therefore, using single-agent dose-finding methods for combination therapies is not appropriate. In recent years, several authors have proposed novel dose-finding designs for combination studies, which use either algorithm-based or model-based methods. The aim of our work was to compare, via a simulation study, six dose-finding methods for combinations proposed in recent years. We chose eight scenarios that differ in terms of the number and location of the true MTD(s) in the combination space. We then compared the performance of each design in terms of correct combination selection, patient allocation, and mean number of observed toxicities during the trials. Our results showed that the model-based methods performed better than the algorithm-based ones. However, none of the compared model-based designs gave consistently better results than the others.

Phase I/IIa study evaluating the safety, efficacy, pharmacokinetics, and pharmacodynamics of lucitanib in advanced solid tumors.

BACKGROUND: Lucitanib is a potent, oral inhibitor fibroblast growth factor receptor types 1 and 2 (FGFR), vascular endothelial growth factor receptor types 1, 2, and 3 (VEGFR), platelet-derived growth factor receptor types α and ß (PGFRα/ß), which are essential kinases for tumor growth, survival, migration, and angiogenesis. Several tumor types, including breast carcinoma, demonstrate amplification of fibroblast growth factor (FGF)-related genes. There are no approved drugs for molecularly defined FGF-aberrant (FGFR1- or FGF3/4/19-amplified) tumors. METHODS: This open-label phase I/IIa study involved a dose-escalation phase to determine maximum tolerated dose (MTD), recommended dose (RD), and pharmacokinetics of lucitanib in patients with advanced solid tumors, followed by a dose-expansion phase to obtain preliminary evidence of efficacy in patients who could potentially benefit from treatment (i.e. with tumors harboring FGF-aberrant pathway or considered angiogenesis-sensitive). RESULTS: Doses from 5 to 30 mg were evaluated with dose-limiting toxic effects dominated by vascular endothelial growth factor (VEGF) inhibition-related toxic effects at the 30 mg dose level (one case of grade 4 depressed level of consciousness and two cases of grade 3 thrombotic microangiopathy). The most common adverse events (all grades, all cohorts) were hypertension (91%), asthenia (42%), and proteinuria (57%). Exposure increased with dose and t½ was 31-40 h, suitable for once daily administration. Seventy-six patients were included. All but one had stage IV; 42% had >3 lines of previous chemotherapy. Sixty-four patients were assessable for response; 58 had measurable disease. Clinical activity was observed at all doses tested with durable Response Evaluation Criteria In Solid Tumors (RECIST) partial responses in a variety of tumor types. In the angiogenesis-sensitive group, objective RECIST response rate (complete response + partial response) was 26% (7 of 27) and progression-free survival (PFS) was 25 weeks. In assessable FGF-aberrant breast cancer patients, 50% (6 of 12) achieved RECIST partial response with a median PFS of 40.4 weeks for all treated patients. CONCLUSION: Lucitanib has promising efficacy and a manageable side-effect profile. The spectrum of activity observed demonstrates clinical benefit in both FGF-aberrant and angiogenesis-sensitive populations. A comprehensive phase II program is planned.

Accuracy of dry vaginal self-sampling for detecting high-risk human papillomavirus infection in cervical cancer screening: a cross-sectional study.

OBJECTIVE: Cervical cancer screening coverage remains insufficient in most countries. Testing self-collected samples for high-risk human papillomavirus (HR-HPV) could be an alternative to the Pap smear, but costs, sampling methods and transport issues hamper its wide use. Our objective was to compare diagnostic accuracy of 2 vaginal self-collection methods, a dry swab (vsc-DRY) or swab in liquid medium (vsc-LIQ), for detecting HR-HPV cervical infection assessed by a cervical clinician-collected sample in liquid medium (ccc-LIQ). METHODS: Women 20 to 65 years attending a Pap smear were recruited between September, 2009 and March, 2011. Each sample (3 per woman) underwent HPV DNA testing. Samples were classified as HR-HPV+ with detection of at least one HR-HPV or probable HR-HPV type. RESULTS: Of 734 women included, 722 had complete HPV data. HR-HPV was detected in 20.9% of ccc-LIQ samples. Estimated sensitivity and specificity to detect HR-HPV in vsc-DRY samples were 88.7% and 92.5%, respectively, and in vsc-LIQ samples, 87.4% and 90.9%. Cytology findings were abnormal for 79 women (10.9%): among 27 samples of low-grade squamous intraepithelial lesions, 25 were HR-HPV+ in vsc-DRY, vsc-LIQ and ccc-LIQ samples. Among 6 samples of high-grade squamous intraepithelial lesions, all were HR-HPV+ in vsc-DRY samples, 1 was HR-HPV- in vsc-LIQ samples and 1 was HR-HPV- in ccc-LIQ samples. CONCLUSIONS: Vaginal self-sampling with a dry swab is accurate to detect HR-HPV infection as compared with cervical clinician-collection and accurate as compared with cytology results. This cheap and easy-to-ship sampling method could be widely used in a cervical cancer screening program.

Non-resonant and non-enhanced Raman correlation spectroscopy.

We present the first non-resonant and non-enhanced Raman correlation spectroscopy experiments. They are conducted on a confocal microscope combined with a Raman spectrometer. The thermal fluctuations of the Raman intensities scattered by dispersions of polystyrene particles of sub-micrometric diameters are measured and analysed by deriving the autocorrelation functions (ACFs) of the intensities. We show that for particles of diameter down to 200 nm, RCS measurements are successfully obtained in spite of the absence of any source of amplification of the Raman signal. For particles of diameter ranging from 200 to 750 nm, the ACFs present a time-decay behaviour in accordance with the model of free Brownian particles. For particles of 1000 nm in diameter, the AFCs present a different behaviour with a much smaller characteristic time. This results from the dynamics of a single-Brownian particle trapped in the confocal volume by the optical forces of the focus spot.

A retrospective case series of 103 consecutive patients with leptomeningeal metastasis and breast cancer.

Approximately 2-5 % of patients with breast cancer (BC) develop leptomeningeal metastasis (LM). 103 consecutive patients with BC were diagnosed with LM and initially treated with intra-CSF liposomal cytarabine from 2007 to 2011 at a single institution. Correlations were determined with respect to patient characteristics and BC subtype with regard to overall survival (OS). At LM diagnosis, 61 % of patients had a 0-2 performance status (PS), the remaining 39 % were severely neurologically impaired. Regardless of PS, all patients received intra-cerebrospinal fluid (CSF) liposomal cytarabine as first-line treatment. Systemic treatment and radiotherapy were also given in 58 and 17 % of patients respectively as clinically appropriate. Second- (intra-CSF thiotepa) and third-line (intra-CSF methotrexate) treatment was administered in 24 and 6 patients respectively. Median OS was 3.8 months (range 1 day-2.8 years). In multivariate analysis, an initial combined treatment, a second-line treatment with intra-CSF thiotepa, an initial clinical response, and a non-'ER/PR/HER2 negative' BC were significantly associated with a better OS. Median OS in this heterogeneous retrospective case series was similar to that of previously observed BC patients treated with intra-CSF methotrexate suggesting intra-CSF liposomal cytarabine is a reasonable first choice therapy of BC-related LM.

Sonic aerosol therapy to target maxillary sinuses.

AIM: Intranasal aerosol administration of drugs is widely used by ENT specialists. Although clinical evidence is still lacking, intranasal nebulization appears to be an interesting therapeutic option for local drug delivery, targeting anatomic sites beyond the nasal valve. The sonic nebulizer NL11SN associates a 100Hertz (Hz) sound to the aerosolization to improve deposition in the nasal/paranasal sinuses. The aim of the present study was: to evaluate in vivo the influence of associating a 100Hz sound on sinus ventilation and nasal and pulmonary aerosol deposition in normal volunteers, and; to quantify in vitro aerosol deposition in the maxillary sinuses in a plastinated head model. MATERIAL AND METHODS: Scintigraphic analysis of (81m)Kr gas ventilation and of sonic aerosol ((99m)Tc-DTPA) deposition using the NL11SN was performed in vivo in seven healthy volunteers. In parallel, NL11SN gentamicin nebulization was performed, with or without associated 100Hz sound, in a plastinated human head model; the gross amount of gentamicin delivered to the paranasal sinuses was determined by fluorescence polarization immunoassay. RESULTS: Associating the 100Hz sound to (81m)Kr gas ensured paranasal sinus ventilation in healthy volunteers. (99m)Tc-DTPA particles nebulized with the NL11SN were deposited predominantly in the nasal cavities (2/3, vs 1/3 in the lungs). In vitro, the use of NL11SN in sonic mode increased gentamicin deposition threefold in the plastinated model sinuses (P<0.002); the resulting antibiotic deposit would be sufficient to induce a local therapeutic effect. CONCLUSION: The NL11SN nebulizer ensured preferential nasal cavity aerosol deposition and successfully targeted the maxillary sinuses.

Full off-axis red-green-blue digital holographic microscope with LED illumination.

We developed a new full off-axis red-green-blue (RGB) digital holographic microscope with an LED illumination. A decisive advantage of the use of LED illumination is a large image quality improvement due to its partially coherent nature. The off-axis configuration enables the fast recording of the holographic data in each spectral channel. The digital holographic refocusing and the optical phase map computation are successfully demonstrated. The multiwavelength operation provides a significant improvement of the collected information for colored samples.

[Evolution and follow-up of hunger strikers: experience from an interregional hospital secured unit]. / Évolution et surveillance des patients grévistes de la faim : expérience d'une unité hospitalière sécurisée interrégionale.

PURPOSE: A hunger strike is a voluntary fast, performed to protest publicly against an issue deemed unfair. In the case of French prisoners, hospitalization in an interregional hospital secured units (UHSI) may be necessary. METHODS: A retrospective epidemiological study based on one UHSI medical records was performed on the period of May, 2006 to December, 2008, and focused on symptoms, outcomes and ethical problems encountered. RESULTS: Seven men and one woman with a mean age of 32.6 years were hospitalized in an UHSI, with nine episodes of hunger strike of a median duration of 57 days. Clinical symptoms began after two weeks of voluntary deprivation in the form of dizziness, weakness, muscle pain and headache. Laboratory tests showed hypoglycemia (<0.4g/L) on admission, 16.3% decrease of albumin after 40.5 days, and dehydration in case of thirst strike. The clinical tolerance was good and no patient presented Wernicke's encephalopathy. A diabetic patient developed acidocetosis during two hunger strikes. All hunger strikes were respected by medical staff, and treatment was based upon surveillance of symptoms, vitamin B and sweetened drinks administration and explanations of the clinical hazards on a daily basis. CONCLUSION: The special problem encountered in the medical management of these strikers was to convince them to accept treatments in order to avoid a coercive life-saving treatment as requested by French law.

Search for a dark matter annihilation signal from the galactic center halo with H.E.S.S.

A search for a very-high-energy (VHE; ≥100 GeV) γ-ray signal from self-annihilating particle dark matter (DM) is performed towards a region of projected distance r∼45-150 pc from the Galactic center. The background-subtracted γ-ray spectrum measured with the High Energy Stereoscopic System (H.E.S.S.) γ-ray instrument in the energy range between 300 GeV and 30 TeV shows no hint of a residual γ-ray flux. Assuming conventional Navarro-Frenk-White and Einasto density profiles, limits are derived on the velocity-weighted annihilation cross section (σv) as a function of the DM particle mass. These are among the best reported so far for this energy range and in particular differ only little between the chosen density profile parametrizations. In particular, for the DM particle mass of ∼1 TeV, values for (σv) above 3×10(-25) cm(3) s(-1) are excluded for the Einasto density profile.