French health insurance data for chronic rhinosinusitis with nasal polyps between 2011 and 2018: A STROBE-compliant analysis.

AIMS: The main aim of the present study was to report the annual volume of surgeries performed for chronic rhinosinusitis with nasal polyps (CRSwNP) in France, based on health insurance data. The secondary objectives were to describe the different characteristics of the surgeries and their complications, and to estimate the number of patients eligible for biotherapy. MATERIAL AND METHODS: This was a descriptive observational retrospective study using data from French national health insurance databases for the period 2011-2018. Inclusion criteria comprised all hospital stays with procedures related to CRSwNP according to the French Common Classification of Medical Acts and consistent with French practices. RESULTS: Ninety-two thousand one hundred and fourty one patients (92,141) for 92,884 admissions for CRSwNP surgery were analyzed, providing an accurate representation of CRSwNP surgery in France between 2011 and 2018. The revision surgery rate for patients operated on in 2011 was 13.0% (1,457/11,212), corresponding to an average annual rate of 1.86% over 7 years. In the 11,750 sinus surgery admissions in 2018, the complications rate was only 0.65% (77/11,750). CONCLUSION: Sinus surgery is safe (0.65% complications) and reliable (estimated revision rate, 5.5%: 5,078/92,884). This study provides the first evaluation of the target population for biotherapy in France.

Pharmacovigilance study of a regional intravenous immunoglobulin (II): evaluation and comparison of an improved pharmaceutical form.

INTRODUCTION: Intravenous immunoglobulin (IVIG) therapy is an effective treatment in patients with different diseases. This product must comply with all the regulatory requirements established by the World Health Organization and the European Pharmacopoeia for clinical tolerance, therapeutic efficacy, and viral safety. Although IVIG are effective and safe products, in some patients they may cause adverse reactions. OBJECTIVES: The aim of this study was to assess the clinical tolerance of two pharmaceutical forms (lyophilized and liquid) of Imunoglobulina G Endovenosa UNC (IVIG UNC), a regional IVIG preparation, and to compare the reported data. PATIENTS AND METHODS: The pharmacovigilance reports of 149 infusions in 51 patients treated with lyophilized IVIG UNC and of 157 infusions in 53 patients treated with liquid IVIG UNC were statistically evaluated. Clinical tolerance was evaluated through the adverse reactions reported. RESULTS: Lyophilized IVIG UNC: adverse reactions were reported in 6.7 % of the total number of infusions. Of these reactions, 4.0 % were mild, 2.0 % were moderate, and 0.7 % severe. Liquid IVIG UNC: adverse reactions were reported in 3.2 % of the total number of infusions; of these, 1.3 % were mild, 1.9 % were moderate, and 0.0 % were severe. Statistical analysis showed no association between tolerance and the pharmaceutical form used (p > 0.05) and indicated similar tolerance for both preparations. CONCLUSIONS: Based on the results obtained, the excellent clinical tolerance of both pharmaceutical forms of IVIG UNC can be confirmed.

[Pharmacovigilance study of a regional intravenous immunoglobulin]. / Estudio de farmacovigilancia de una inmunoglobulina endovenosa regional.

BACKGROUND: Intravenous immunoglobulin preparations are an effective therapy in several processes: primary and secondary immunodeficiencies, autoimmune and inflammatory disorders, infectious diseases and allergies, among others. This biological medicine must comply with three conditions: clinical tolerance, therapeutic efficacy and viral safety. OBJECTIVES: The aim of this study was to assess the therapeutic efficacy, clinical tolerance and viral safety of a regional intravenous immunoglobulin, manufactured by the Hemoderivatives Laboratory of the National University of Cordoba in Argentina (Inmunoglobulina G Endovenosa UNC), with plasma obtained from voluntary, unremunerated donors from Argentina, Chile and Uruguay. PATIENTS AND METHODS: The pharmacovigilance records of 448 infusions in 111 patients with different diseases were statistically evaluated. Clinical tolerance was evaluated by recording of adverse events, therapeutic efficacy was evaluated by taking into account the specific parameters of each disease, and viral safety was evaluated by analysis of serological markers of hepatitis B, hepatitis C and human immunodeficiency viruses before and after infusion. RESULTS: Adverse effects were observed in 4.6 % of total infusions, of which 3.1 % were mild, 1.3 were moderate and 0.2 % were severe. The therapeutic efficacy of the product was recorded in all diseases in which it was administered. Regarding viral safety, no seroconversions were registered in any of the records evaluated. CONCLUSIONS: The results of this study indicate that Inmunoglobulina G Endovenosa UNC is well tolerated, with good therapeutic efficacy and viral safety.

Effect of surgical trauma on various aspects of the immune response in rats.

The effects of a standard laparotomy on different aspects of the immune response were studied in Wistar R/A rats. When the antigen was administered at the time of operation, antibody synthesis against sheep red blood cells (SRBC), a thymo-dependent antigen was significantly stimulated. The same phenomenon was observed when a soluble antigen extracted from SRBC was injected during the surgical procedure. On the contrary, late antibody production induced by formalinized Salmonella enteritidis or Escherichia coli lipopolysaccharide, two thymo-independent antigens, was reduced in operated animals. Cell-mediated immunity against SRBC was investigated by the radiometric ear index test described by Kostiala in 1977. Surgery did not alter the induction phase but suppressed the expression of the cellular immune response. Carrageenin-induced edema was inhibited in operated rats. These results show that surgical trauma acts differently on the various aspects of the immune response.

Effect of surgical trauma on delayed type hypersensitivity.

There is no general agreement in the literature concerning the effects of surgery on delayed type hypersensitivity (DTH). Therefore, the effect of a standard laparotomy on DTH was studied in rats and measured by the ear index method of Kostiala. Surgery depresses significantly the ear index in animals challenged at the time of operation (2.35 +/- 0.24 vs 6.30 +/- 1.26) or 24 hr later (2.69 +/- 0.21 vs 4.34 +/- 0.64). There is no late rebound of the immune response. The reduction of ear index is not due to a delayed response of operated rats but is really a decrease of the peak response. Surgery seems to act on the early phase of the immune response.

Effect of surgical procedures on the humoral responsiveness of rats.

The humoral response after an intravenous injection of 10(9) sheep red blood cells was studied in a control group of rats and in rats submitted to three types of surgical procedures. The operated upon rats had an increased antibody synthesis, and this enhancing effect seemed to be proportional to the intensity of surgical trauma. The stimulatory effect of operation was also observed when the antigen was administered in the operative field.

Kinetics of humoral responsiveness and antigenic distribution in operated rats.

Wistar R/A rats were injected intravenously with 10(9) sheep red blood cells (SRBC) prior to, during or after a standard laparotomy. Stimulation of anti-SRBC antibody synthesis was already observed when the antigen was given 4 h prior to surgery and was maximal if SRBC were administered at the time of operation. The enhancing effect on the immune response lasted for 2 days after surgery. From the third post-operative day on, the injection of SRBC induced a normal humoral response. No subsequent depression was detected. Inter-organ distribution studies of 51Cr-labelled SRBC injected at various times prior, during or after the surgical procedure, showed a maximum decrease of liver uptake during operation; the depression was still present 2 h later but on the first post-operative day, no significant difference from the controls could be demonstrated. When the labelled antigen was given before surgery, organ distribution was normal. Consequently, there is no time relationship between the stimulation of antibody production and the alteration of total phagocytosis induced by surgery. Therefore, the enhanced humoral response cannot be explained only by spillover of the antigen from the liver into lymphoid organs.

Stimulation of antibody synthesis induced by surgical trauma in rats.

The effect of a standard laparatomy on antibody synthesis was studied in Wistar R/A rats recieving an intravenous injection of 10(9) sheep red blood cells (SRBC) during the surgical procedure. Anti-SRBC antibody titres were significantly higher in operated animals than in controls. When SRBC were given 2 hr after the surgical procedure, stimulation of antibody synthesis still persisted, but when the antigen was administered 24 hr after laparotomy, no significant difference could be detected between the operated animals and controls. Surgery also enhances the secondary humoral response.

[Presence of soluble red cell antigens in antilymphocyte serum or in serum of normal rabbits absorbed with sheep red cells (author's transl)]. / Présence d'antigènes érythrocytaires solubles dans le sérum antilymphocyte ou le sérum de lapin normal absorbé avec des globules rouges de mouton

The treatment of Wistar rats with normal rabbit sera or rabbit anti-Rat lymphocyte sera preabsorbed with sheep red blood cells induces variable degrees of immunisation against these erythrocytes. This phenomenon is due to transfer of soluble erythrocyte antigen released during the absorption procedure.

Organ distribution of sheep red blood cells in ALS-treated rats.

The inter-organ distribution of radioactivity in rats injected with 51Cr-labelled SRBC is altered after treatment with ALS absorbed with this antigen. The alteration is due to the presence of soluble SRBC antigens in the serum and subsequent immunization of the tested animals. The 51Cr distribution does not correspond to the uptake of antigenic material in immunized rats.