[Feedback on clinical oncology pharmacy]. / Retour d'expérience en pharmacie clinique oncologique.

The rising of oral anticancer therapies let more and more patients to be cared at home and improve their quality of life. However the toxicities of these drugs and the distance with health professionals imply that the patient needs to be more autonomous with respect to his treatment. Patients through therapeutic education programs allows them to manage side effects, to be more observant and then to subsequently benefit from the treatment. We report here, oncology clinical pharmacists experiences in some health facilities in France, presented at the 1st day of clinical oncology pharmacy (December 2017, Marseille).

(97)(37)Rb(60): The Cornerstone of the Region of Deformation around A ∼ 100 [corrected].

Excited states of the neutron-rich nuclei (97,99)Rb were populated for the first time using the multistep Coulomb excitation of radioactive beams. Comparisons of the results with particle-rotor model calculations provide clear identification for the ground-state rotational band of (97)Rb as being built on the πg(9/2) [431] 3/2(+) Nilsson-model configuration. The ground-state excitation spectra of the Rb isotopes show a marked distinction between single-particle-like structures below N=60 and rotational bands above. The present study defines the limits of the deformed region around A∼100 and indicates that the deformation of (97)Rb is essentially the same as that observed well inside the deformed region. It further highlights the power of the Coulomb-excitation technique for obtaining spectroscopic information far from stability. The (99)Rb case demonstrates the challenges of studies with very short-lived postaccelerated radioactive beams.

[Dementia: Where are the Lewy bodies?]. / Démences : où sont les corps de Lewy ?

Dementia with Lewy bodies (DLB) is the second cause of degenerative dementia in autopsy studies. In clinical pratice however, the prevalence of DLB is much lower with important intercenter variations. Among the reasons for this low sensitivity of DLB diagnosis are (1) the imprecision and subjectivity of the diagnostic criteria; (2) the underestimation of non-motor symptoms (REM-sleep behavior disorder, dysautonomia, anosmia); mostly (3) the nearly constant association of Lewy bodies with Alzheimer's disease pathology, which dominates the clinical phenotype. With the avenue of targeted therapies against the protein agregates, new clinical scales able to apprehend the coexistence of Lewy pathology in Alzheimer's disease are expected.

Adherence with oral oncologic treatment in cancer patients: interest of an adherence score of all dosing errors.

PURPOSE: Patient nonadherence to oral antineoplastic therapy is a well-recognized barrier to effective treatment. In order to identify patients who may need additional support to become adherent, it is important to have a useful tool that takes into account all the parameters of adherence to prescription. The aim of this prospective study was to evaluate adherence of oral antineoplastic agents and to investigate two calculation methods of adherence score. PATIENTS AND METHODS: Twenty-nine cancer patients were enrolled in this study. Fourteen were treated by capecitabine and 15 patients by aromatase inhibitors. Adherence was measured using a medication event monitoring system and adherence score was calculated by a usual method and a composite adherence score that takes into account missed doses and also intake interval errors (between 2 doses and between meals). RESULTS: Across the 6-month evaluation period, average adherence was 95% with the standard calculation (capecitabine group: 89%; aromatase inhibitor group: 99%) versus 83% with the composite index (capecitabine group: 62%; aromatase inhibitor group: 99%) (p = 0.030). The composite calculation permits to highlight more nonadherent patients (29.6 vs. 7.4%), particularly in the capecitabine group (73 vs. 18%, p = 0.001). We report 2 cases identified as nonadherent with composite adherence rate. CONCLUSION: The composite adherence score permits to better evaluate adherence to prescription and to identify barriers to adherence and persistence.

Unveiling the intruder deformed 02(+) state in 34Si.

The 02(+) state in 34Si has been populated at the GANIL-LISE3 facility through the ß decay of a newly discovered 1(+) isomer in 34Al of 26(1) ms half-life. The simultaneous detection of e(+)e(-) pairs allowed the determination of the excitation energy E(02(+))=2719(3) keV and the half-life T(1/2)=19.4(7) ns, from which an electric monopole strength of ρ(2)(E0)=13.0(0.9)×10(-3) was deduced. The 2(1)(+) state is observed to decay both to the 0(1)(+) ground state and to the newly observed 0(2)(+) state [via a 607(2) keV transition] with a ratio R(2(1)(+)→0(1)(+)/2(1)(+)→0(2)(+))=1380(717). Gathering all information, a weak mixing with the 0(1)(+) and a large deformation parameter of ß=0.29(4) are found for the 0(2)(+) state, in good agreement with shell model calculations using a new SDPF-U-MIX interaction allowing np-nh excitations across the N=20 shell gap.

Is the 7/2(1)- isomer state of 43S spherical?

We report on the spectroscopic quadrupole moment measurement of the 7/2(1)(-) isomeric state in (16)(43)S(27) [E*=320.5(5) keV, T(1/2)=415(3) ns], using the time dependent perturbed angular distribution technique at the RIKEN RIBF facility. Our value, |Q(s)|=23(3) efm(2), is larger than that expected for a single-particle state. Shell model calculations using the modern SDPF-U interaction for this mass region reproduce remarkably well the measured |Q(s)|, and show that non-negligible correlations drive the isomeric state away from a purely spherical shape.

Electromagnetic transition rates in 100,101Pd using the Recoil Doppler Shift Technique.

The quadrupole deformations for the low-lying states in the transitional nuclei 100,101Pd have been deduced through the measurement of their electric quadrupole transition probabilities using the Recoil Distance Doppler Shift Method. The nuclei were studied using a 268 MeV 80Se beam impinging on a thin, self-supporting 24Mg target. States in 100Pd and 101Pd populated by the four and three neutron evaporation channels respectively, with reaction gamma-rays detected using the SPEEDY gamma-ray detection array. The recoiling nuclei were stopped in a copper foil and gamma-ray coincidence data taken at 10 separate target-stopper distances between 35 µm and 750 µm. The mean-lifetimes for the lowest lying 2+ (in 100Pd) and 15/2- (in 101Pd) states were measured to be 13.3(9) ps and 10.8(8) ps respectively. These data are compared with predictions from nuclear Total Routhian Surface calculations, which are found to agree with the experimentally deduced values to within 10%.

Clinical features distinguishing angle closure from pseudoplateau versus plateau iris.

PURPOSE: To evaluate clinical aspects of patients with the diagnosis of plateau iris (PI) or pseudoplateau iris (PPI) made by ultrasound biomicroscopy (UBM) in order to determine if there are any clinical factors that can help differentiate between these two entities. METHOD: A retrospective cohort of consecutive UBM patients with the diagnosis of PI or PPI. The diagnosis of PI was based on an anteriorly positioned ciliary body that abutted the peripheral iris, a narrow (<10 degrees) or closed angle for at least 180 degrees, and the anterior portion of the iris positioned anterior to scleral spur. The diagnosis of PPI was similar to plateau except that large or a cluster of small cysts had to be present in the iridociliary sulcus. RESULTS: There were a total of 76 patients (29% male), 21 with PPI and 55 with PI. Patients with PPI were more likely to be male (p = 0.005), slightly younger (51.5 (SD 10.7) vs 57.9 (10.2) p = 0.0190), have a "bumpy" peripheral iris appearance (p = 0.003), have greater trabecular meshwork pigmentation (2.0 (0.7) vs 1.3 (0.6) p = 0.004) and have fewer clock hours of gonioscopic angle closure versus plateau iris patients (5.1 (4.3) vs 9.2 (4.2) p = 0.0009). Spherical equivalent was not significantly different between groups (0.50D (1.69) PPI vs 1.33D (2.42) PI; p = 0.187). CONCLUSIONS: In patients being referred to a UBM clinic for evaluation of angle-closure mechanism, younger males with a bumpy peripheral iris have a higher likelihood of having a diagnosis of pseudoplateau iris. However, clinical factors do not appear to discriminate well between PPI and PI. UBM is extremely helpful in confirming underlying mechanism and guiding therapy.

[Therapeutic potential of melatonin in cancer treatment]. / Potentiel thérapeutique de la mélatonine dans la prise en charge de la pathologie cancéreuse.

Melatonin is a small lipophile molecule, essentially secreted by pineal gland. The synthesis of this hormone shows a circadian pattern with a peak around 2-3 hours am. Many melatonin receptors are found in the body, which explains its multiple functions as biological rhythms resynchronisation, sleep induction, vasoregulation and even immunomodulation. Many experiments realised in this field have permit to discover different interactions between melatonin and the immune system, and especially the link which exists between melatonin and the fight against cancer via the immune system. Phase II studies reported a decrease of thrombocytopenia, an increase of some cytokines rate and an increase of objective responses in cancer patients. In order to confirm these results and to lead further research, we propose to realise a phase II randomised study melatonin versus placebo in metastatic breast cancer patients after two lines of treatment.

[Stress, cancer and circadian rhythm of melatonin]. / Stress, cancer et rythme circadien de la mélatonine.

Influence of stress on immunity and pathogenesis relates to corticotropic axis: hypothalamus-hypophysis-surrenals (HHS). Its over-stimulation due to traumas during early childhood or before birth seems to generate brain abnormalities such as reduction of hippocampus volume. More typical of adult age, hypothalamus-pineal gland axis (HP), responsible for melatonin production, may be impaired because of chronic stress, mainly through sleep disturbances or addictive behaviours. Old age has been reported to produce same impairments. Circadian cycle of melatonin is closely related to immune functions and its disturbance seems to induce, among populations undergoing frequent changes of life rhythm, a significant raise of cancer incidence: night shift workers, air pilots... Stress then seems enable to increase cancer risk through its negative impact on HHS and HP axis and therefore on immunity. Immunotherapy, which was an interesting solution considering this, has not yield yet expected results. Upstream, other ways have been successfully investigated in prospective randomised trials, such as psychotherapeutic treatments, with positive effects on cellular immunity and survival. The ability to condition immune responses in animals allows thinking that hypnotherapy could also be used along with standard treatments.

[Modeling 5-FU clearance during a chronomodulated infusion]. / Modélisation de la clairance du 5-FU pendant une perfusion chronomodulée.

Drugs pharmacokinetic control is a usual practice in case of flat continuous infusions. It enables among others, to modulate delivered doses when drug concentrations in blood appear too high. With chronotherapy, this possibility becomes more difficult because of sinusoidal outflows of infusion. We propose here a method that enables this follow-up, established through the study of 21 metastatic colorectal cancer patients, treated with a chronomodulated infusion of high dose 5-fluoro-uracil (5-FU) and folinic acid. This pharmacokinetic follow-up permitted the modelisation of 5-FU clearance and the calculation of an index, which was, in our study, correlated to the treatment response and also to main encountered toxicities.

Familial occurrence of pseudoexfoliation in Canada.

BACKGROUND: Genetic factors may play an important role in pseudoexfoliation syndrome. We describe the familial occurrence of pseudoexfoliation in Canadian families. METHODS: Probands with pseudoexfoliation were referred to a tertiary care glaucoma service in Ottawa because of a family history of pseudoexfoliation or glaucoma, or both. Probands and family members who agreed to participate underwent a systematic interview and eye examination. The pseudoexfoliation status was classified as affected, suspect or unknown based on preestablished criteria for the diagnosis of pseudoexfoliation and glaucoma. RESULTS: Thirty-four members of 10 families were assessed (18 affected, 2 suspect and 14 status unknown). Six families had two or more generations with pseudoexfoliation, and four families had one generation affected. There was a predominance of females among the affected subjects (17:1), and transmission in all cases appeared to be maternal. Eight of the families were of Irish/Scottish ancestry. Nine (50%) of the affected subjects had cardiovascular disease. Affected subjects tended to be older than suspects and those whose status was unknown (mean age 77, 67 and 55 years respectively). Seven subjects were affected unilaterally and 11 bilaterally. Affected subjects had moderate angle pigmentation in both eyes (mean +2.7, where 0 = no pigment and +4 = dense homogeneous pigment). The mean intraocular pressure in both eyes was higher for the affected subjects (23.1 [standard deviation (SD) 8.6] mm Hg) than for the suspects (16.8 [SD 6.1] mm Hg) and those of unknown status (16.8 [SD 2.9] mm Hg). An enlarged cup:disc ratio was seen in the affected subjects (mean 0.62). Eleven (61%) of the affected subjects had open angles on gonioscopy, and five had occludable angles and required peripheral iridectomy. Ten (56%) of the affected subjects were classified as having glaucoma, and 14 (78%) had evidence of cataract formation in at least one eye. INTERPRETATION: Pseudoexfoliation appears to be transmitted matrilineally, which raises the possibility of mitochondrial inheritance, X-linked inheritance or autosomal inheritance with genomic imprinting. A larger study of families with pseudoexfoliation is necessary to clarify the mode of transmission and to identify the gene(s) involved in the etiology of this disorder.

Apraclonidine 0.5% versus brimonidine 0.2% for the control of intraocular pressure elevation following anterior segment laser procedures.

BACKGROUND AND OBJECTIVE: Both apraclonidine hydrochloride 0.5% and brimonidine tartrate 0.5% are potent alpha-2 agonists, effective in controlling the intraocular pressure (IOP) rise following argon laser trabeculoplasty (ALT). Brimonidine has recently become available commercially as a 0.2% solution. Our goal in this study was to compare the efficacy and side effect profile of 0.2% brimonidine to that of 0.5% apraclonidine in the prevention of IOP spikes following anterior segment laser procedures. PATIENTS AND METHODS: Patients undergoing argon laser trabeculoplasty, Nd:Yag peripheral iridectomy or posterior capsulotomy were prospectively randomized to receive either apraclonidine 0.5% or brimonidine 0.2%, approximately 10 minutes prior to laser surgery. Intraocular pressure was measured by a masked observer, using Goldmann applanation tonometry, before and 1 hour after the treatment. RESULTS: 51 ALTs, 21 peripheral iridectomies, and 13 posterior capsulotomies were performed. The incidence of an IOP rise greater than 5 mmHg was 3/43 (7.0%) in the brimonidine group and 0/42 (0%) in the apraclonidine group (P = 0.08, chi-squared). There were no IOP elevations greater than 8 mmHg. All IOP rises of greater than 5 mmHg occurred in the ALT sub-group, and within this sub-group, the mean change in IOP from pre- to post-op was -4.00 +/- 5.87 in the brimonidine group versus -4.29 +/- 3.86 in the apraclonidine group (P = 0.84). There was a statistically significant decrease in IOP from baseline in both drug groups (P < .0001). CONCLUSIONS: Both drugs are highly effective in controlling IOP spikes following anterior segment laser procedures. There is a tendency toward higher risk of IOP rise following argon laser trabeculoplasty with 0.2% brimonidine as compared to 0.5% apraclonidine, however, this was not statistically significant.

[Analysis of hematopoietic growth factor prescriptions in 19 french cancer centers]. / Analyse de la prescription de facteurs de croissance hématopoïétique dans 19 centres anticancéreux français. Groupe de pharmaciens de la Fédération nationale des centres de lutte contre le cancer.

Medical prescription of hematopoietic growth factors (HGF) was analysed in 19 anticancer french centers during 2 months. About 4% of anticancer chemotherapeutic cycles prescribed during this period were supported by HGF prescription. The mean duration of treatment was 8 days. Among the 755 collected prescriptions, two tumor localizations represented about 50% of the prescriptions: malignant non Hodgkin lymphomas and breast cancer. The other main localizations concerned adult or pediatric soft tissue sarcomas (18%), testicular cancer (7%) and gynecologic tumors (6%). The prescription for primary prophylaxis for febrile neutropenia remains the main use of HGF (44%). The respect of the guidelines established by the F|d|ration nationale des centres de lutte contre le cancer was analyzed. Overall, 66% of the prescriptions were in adequation with these guidelines. Whereas the consommation of HGF decreased in the 19 considered institutions, it did not reach a plateau and could decrease in institutions which are awaked to the international and national recommendations.

Stability and compatibility of a mixture of the anti-cancer drugs etoposide, cytarabine and daunorubicine for infusion.

We evaluated (i) the stability of a mixture of the three anti-cancer agents used for the treatment of leukemia, namely etoposide, cytarabine and daunorubicine, in 5% glucose, and (ii) its compatibility towards various materials during an infusion protocol as performed for therapeutic purposes in hospital practice. Etoposide and cytarabine were assayed by high-performance liquid chromatography with a C18 type column and UV detection. Daunorubicine was assayed by visible spectrophotometry. The stability study showed all three anti-cancer drugs to be stable in 5% glucose solution, both alone and mixed. Best conservation was obtained by keeping bottles containing the mixture in the dark at room temperature. During the infusion protocol used in clinical practice, etoposide, cytarabine and daunorubicine were stable and compatible with the various materials present in the infusion sets and extension tubing (polyvinyl chloride, polyethylene) and catheters (silicone). Observed variations in concentration did not exceed 10% of initial concentrations of each drug, though we would advocate changing infusion sets and extension tubing daily.

[Primary uretero-vesical malposition without radiological reflux (author's transl)]. / Les malpositions urétéro-vésicales primitives sans reflux radiologique.

Amongst a series of 190 cases of unilateral vesico-ureteric reflux detected by cystography, 94 children had a contralateral malformation identical to that where there was radiological reflux. They underwent a bilateral anti-reflux operation which in the majority of cases prevented any recurrence of acute pyelonephritis. The authors add a series of 18 cases of children who had suffered from several episodes of acute pyelonephritis without it being possible to demonstrate the radiological existence of vesico-ureteric reflux and in whom there was no obstructive disorder or lithiasis of the upper urinary tract. Nine of these patients showed corticopapillary involvement (unilateral in 8, bilateral in 1) similar to that seen in children with cystographic reflux. All the children of the group had a malformation of uretero-vesical implantation similar to that seen in the other children with cystographic reflux. After antireflux surgery (unilateral in 3 cases and bilateral in 15), almost all the children were free of further episodes of acute pyelonephritis. In the opinion of the authors, these two series of surgical patients validate the individualisation of this special group of "reflucing uretero-vesical malpositions without radiological reflux".