Evaluation of the care pathway in the context of the dispensing of emicizumab (Hemlibra) in community and hospital pharmacies in France: A patient satisfaction survey

Introduction

Since June 2021 in France, patients with haemophilia A with anti-factor VIII inhibitors and patients with severe haemophilia A without anti-factor VIII inhibitors, and treated with emicizumab (Hemlibra), have to choose the dispensing circuit community or hospital pharmacy.

Aim

To evaluate satisfaction of patients whether they choose dispensation from a community pharmacy or retained dispensation from the hospital pharmacy, to understand the main motivation for choosing the community or the hospital pharmacy.

Methods

All patients living in France, regardless of age, were eligible to participate. Between September 13, 2022, and January 9, 2023, 175 respondents answered the satisfaction survey, including 123 in community pharmacy and 52 in hospital pharmacy.

Results

Eighteen months after availability in community pharmacies, treatment accessibility is improved for the benefit of the patient. The door-to-door travel times are significantly reduced to the community pharmacy with an average gain of 16.5 min saved from the place of residence. Patients are mostly satisfied with the new dispensing circuit especially concerning the overall satisfaction (p < .0001), the travel time (p < .0001) and the strong relationship with the pharmacist (p = .0022) compared to hospital pharmacy.

Conclusion

Innovation in care pathways is showing its full potential in improving access to medication, made possible by the implementation of a rigorous organization accompanied by training to enable healthcare professionals involved in primary care to provide appropriate management.     

New portable optical sensors for the assessment of winegrape phenolic maturity based on berry fluorescence

Grape phenolic maturity is usually assessed by destructive wet chemistry in the laboratory. Yet, for precision agriculture or continuous monitoring of maturation, more rapid and non-destructive methods are needed. Therefore, in addition to measurements of fruit colour, a new optical method was recently proposed. It is based on the screening of fruit chlorophyll fluorescence that allows both flavonol and anthocyanin contents of intact berry skin to be measured. Here, we present the first results obtained with two commercial devices, Dualex FLAV™ and Dualex ANTH™, and a prototype, Multiplex, all based on this new method. We found that the non-contact optical sensor Multiplex has strong potential for an application in the vineyard for precision viticulture or for crop evaluation at the weighbridge.     

A prospective randomized controlled study of phototherapy using blue and blue-green light-emitting devices, and conventional halogen-quartz phototherapy.

OBJECTIVE: To determine the efficacy of blue versus blue-green phototherapy using new light sources with narrow luminous spectra. The devices made of high-intensity gallium nitride light-emitting diodes (LEDs) were also compared to conventional halogen-quartz bulbs phototherapy. DESIGN: Prospective open randomized study. PARTICIPANTS: A total of 114 jaundiced, but otherwise healthy term infants who met the entry criteria for phototherapy set by the American Academy of Pediatrics' Practice Parameter. MAIN OUTCOME MEASURES: The duration of phototherapy and the rate of decrease in total serum bilirubin (TSB). RESULTS: The mean TSB concentrations at initiation and termination of treatment, as well as the duration of phototherapy and the rate of decrease in TSB, were not statistically different in newborns receiving blue LED, blue-green LED or conventional phototherapy. The average rate of decrease in TSB (slope), after adjustment by a linear regression analysis for confounding factors, was -3.61 micromol/hour (95% confidence limits -5.47, -1.75) in the 25 newborns receiving blue LED phototherapy compared with -2.57 micromol/hour (-4.32, -0.82) in the 22 newborns treated with blue-green LED phototherapy and -3.42 micromol/hour (-5.02, -1.81) in the 57 newborns who received conventional phototherapy. CONCLUSIONS: When using low light irradiance, there was no statistically significant difference in the effectiveness of phototherapy using blue-green LEDs, blue LEDs or conventional halogen-quartz bulbs.     

The radial tunnel syndrome

Summary The authors present their experience with 35 cases of radial tunnel syndrome, which is caused by compression of the posterior interosseus nerve in the proximal dorsal forearm related to exertion. Chronic aching muscle pain is the problem. Real paralysis is very rare, and is usually considered as a separate entity. The syndrome is often confused with tennis elbow, although the patient may have both problems. The diagnosis remains clinical, and surgical decompression of the nerve in the region of the supinator will give relief in most cases.

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Résumé Les auteurs présentent leur expérience de 35 cas de syndrome du tunnel radial, causé par la compression du nerf interosseux postérieur à la partie proximale de la face dorsale de l'avantbras, en rapport avec l'exercice physique. Une douleur musculaire chronique et lancinante résume la symptomatologie. La paralysie réele est très rare et est généralement considérée comme une entité distincte. Le syndrome est souvent confondu avec une épicondylite externe, bien que le patient puisse présenter les deux affections. Le diagnostic repose sur l'examen clinique. La décompression chirurgicale du nerf dans la région du muscle court supinateur entraîne un soulagement dans la plupart des cas.

     

Diversity of Francisella tularensis Schu4 antigens recognized by T lymphocytes after natural infections in humans: identification of candidate epitopes for inclusion in a rationally designed tularemia vaccine

The T lymphocyte antigens, which may have a role in protection against tularemia, were predicted by immunoinformatics analysis of Francisella tularensis Schu4. Twenty-seven class II putative promiscuous epitopes and 125 putative class I supertype epitopes were chosen for synthesis; peptides were tested in vitro for their ability to bind HLA and to induce immune responses from PBMCs of 23 previously infected subjects. While the immune responses of individual subjects showed heterogeneity, 95% of the subjects responded strongly to a pool of 27 promiscuous peptides; 25%, 33%, and 44% of subjects responded to pools of 25 A2, A24, and B7 peptides, respectively. These data can aid in the development of novel epitope-based and subunit tularemia vaccines.     

DIET AND TISSUE GROWTH : V. THE EFFECT OF DIETARY PROTEIN ON THE REMAINING KIDNEY OF ADULT WHITE RATS FOLLOWING A UNILATERAL NEPHRECTOMY.

The effects of the ingestion of diets containing different concentrations of protein on the remaining kidney in adult white rats after a unilateral nephrectomy has been studied. In the animals on the high protein diet (85 per cent casein), actual glomerular and tubular lesions were observed in the kidneys of animals maintained for 90, 120 and 150 days after nephrectomy. In the animals on the standard ration, 18 per cent casein, no significant renal lesions were observed within the experimental period. Spontaneous focal lesions in the kidneys of rats maintained on Sherman''s diets "A" and "B" were inconspicuous at the age of 350 days but became progressively more frequent and were commonly observed after 500 days. The animals on the high protein and standard rations were all under 350 days old at the completion of the experiment. It is suggested that the age factor is of importance in that young animals may have greater powers of adaptation in withstanding the injurious effect of high protein rations. The animals on the high protein ration excreted definitely larger quantities of protein in the urine, and showed a higher incidence of casts in periods roughly corresponding to those in which anatomic lesions were observed than did the rats on the standard diet.     

Immunolocalization of the multi-sarco/endoplasmic reticulum Ca2+ATPase system in human platelets

We recently identified a multi-SERCA (sarco/endoplasmic reticulum Ca²⁺ ATPase) system in haemopoietic cells comprising the SERCA 2b, SERCA 3 and a new monoclonal anti-Ca²⁺ ATPase antibody (PL/IM 430) recognizable SERCA isoforms. We have now investigated the subcellular localization of these enzymes in human platelets by Western blotting of subcellular membrane fractions and by immunoelectron microscopy. We precisely defined the recognition specificity of the polyclonal anti-SERCA 2b, anti-SERCA 3, anti-SERCA 1 antibodies as well as of the monoclonal antibody PL/IM 430 by testing their recognition of the tryptic fragments of the SERCA isoforms. The analysis of fragmented membranes enriched in plasma membrane and intracellular membrane components by Western blotting showed that the SERCA 2b and the SERCA 3 isoforms were found in both the plasma membrane and the intracellular membrane fractions, whereas the PL/IM 430 recognizable SERCA isoform was restricted to membranes associated with the plasma membrane fraction. The immunoelectron microscopical study of the SERCA isoforms in resting platelets showed that: (i) the SERCA 2b isoform was expressed in membranes associated with the plasma membrane and open canalicular system, some α-granules and in unidentified membranes; (ii) the SERCA 3 isoform was found associated with plasma and intracellular membranes; and (iii) the PL/IM 430 recognizable SERCA isoform was observed only in structures associated with the cytoplasmic face of the plasma membranes, as confirmed by flow cytometry. Finally, since the PL/IM 430 antibody was raised against intracellular membranes, we looked for a potential membrane redistribution during the isolation procedure used for the preparation of the immunizing membranes. Neuraminidase treatment indeed induced a translocation of the PL/IM 430 recognizable SERCA isoform from plasma to intracellular membranes. Thus, the multi-SERCA system in platelets: (i) is distributed over different platelet membranes, (ii) presents a sub-compartmental organization with some overlapping, and (iii) is partly associated with motile membranes, reflecting an unrecognized level of complexity of Ca²⁺ stores in these cells.     

Clinical and genomic analysis of a randomised phase II study evaluating anastrozole and fulvestrant in postmenopausal patients treated for large operable or locally advanced hormone-receptor-positive breast cancer

Background:

The aim of this study was to assess the efficacy of neoadjuvant anastrozole and fulvestrant treatment of large operable or locally advanced hormone-receptor-positive breast cancer not eligible for initial breast-conserving surgery, and to identify genomic changes occurring after treatment.

Methods:

One hundred and twenty post-menopausal patients were randomised to receive 1 mg anastrozole (61 patients) or 500 mg fulvestrant (59 patients) for 6 months. Genomic DNA copy number profiles were generated for a subgroup of 20 patients before and after treatment.

Results:

A total of 108 patients were evaluable for efficacy and 118 for toxicity. The objective response rate determined by clinical palpation was 58.9% (95% CI=45.0–71.9) in the anastrozole arm and 53.8% (95% CI=39.5–67.8) in the fulvestrant arm. The breast-conserving surgery rate was 58.9% (95% CI=45.0–71.9) in the anastrozole arm and 50.0% (95% CI=35.8–64.2) in the fulvestrant arm. Pathological responses >50% occurred in 24 patients (42.9%) in the anastrozole arm and 13 (25.0%) in the fulvestrant arm. The Ki-67 score fell after treatment but there was no significant difference between the reduction in the two arms (anastrozole 16.7% (95% CI=13.3–21.0) before, 3.2% (95% CI=1.9–5.5) after, n=43; fulvestrant 17.1% (95%CI=13.1–22.5) before, 3.2% (95% CI=1.8–5.7) after, n=38) or between the reduction in Ki-67 in clinical responders and non-responders. Genomic analysis appeared to show a reduction of clonal diversity following treatment with selection of some clones with simpler copy number profiles.

Conclusions:

Both anastrozole and fulvestrant were effective and well-tolerated, enabling breast-conserving surgery in over 50% of patients. Clonal changes consistent with clonal selection by the treatment were seen in a subgroup of patients.