IVIg therapy in the management of BK virus infections in pediatric kidney transplant patients.

BK virus-associated nephropathy (BKPyVAN) induces kidney allograft dysfunction. Although decreasing immunosuppression is the standard for managing BK virus (BKPyV) infection, this strategy is not always effective. The use of polyvalent immunoglobulins (IVIg) may be of interest in this setting. We performed a retrospective single-center evaluation of the management of BKPyV infection in pediatric kidney transplant patients. Among the 171 patients who underwent transplantation between January 2010 and December 2019, 54 patients were excluded (combined transplant n = 15, follow-up in another center n = 35, early postoperative graft loss n= 4). Thus, 117 patients (120 transplants) were included. Overall, 34 (28%) and 15 (13%) transplant recipients displayed positive BKPyV viruria and viremia, respectively. Three had biopsy-confirmed BKPyVAN. The pre-transplant prevalence of CAKUT and HLA antibodies was higher among BKPyV-positive patients compared to non-infected patients. After the detection of BKPyV replication and/or BKPyVAN, the immunosuppressive regimen was modified in 13 (87%) patients: either by decreasing or changing the calcineurin inhibitors (n = 13) and/or switching from mycophenolate mofetil to mTor inhibitors (n = 10). Starting IVIg therapy was based on graft dysfunction or an increase in the viral load despite reduced immunosuppressive regimen. Seven of 15(46%) patients received IVIg. These patients had a higher viral load (5.4 [5.0-6.8]log vs. 3.5 [3.3-3.8]log). In total, 13 of 15 (86%) achieved viral load reduction, five of seven after IVIg therapy. As long as specific antivirals are not available for the management of BKPyV infections in pediatric kidney transplant patients, polyvalent IVIg may be discussed for the management of severe BKPyV viremia, in combination with decreased immunosuppression.

[Patient care pathway and securing immunoglobulin supplies in primary immunodeficiency: Results of a pilot study]. / Parcours de soins du patient et sécurisation des approvisionnements en immunoglobulines dans les déficits immunitaires primitifs : résultats d'une étude pilote.

OBJECTIVES: Securing the supply of immunoglobulins is essential in indications without therapeutic alternatives, such as primary immunodeficiencies (PIDs). The objective was to obtain an inventory of patients with PID, and to quantify their immunoglobulin needs. METHODS: The retrospective study was conducted using data from January to June 2018, in Bordeaux, Lyon and Paris (Saint-Louis). Patients with PID were included based on the pharmaceutical traceability of the 3 centres. The concordance between the patients included and the patients in the CEREDIH register was analysed. RESULTS: For the 361 patients included (sex ratio: M/F 0.8; mean age: 45±20years, mean weight: 62±19kg), 2082 dispensations were performed for a total volume of 57kg of immunoglobulins. Of the 108 specialty changes identified, 68% were due to supply tensions. In total, the analysis of CEREDIH data made it possible to identify 727 patients with PID and followed up once in the study centres, 161 of whom were recorded in the 2 data follow-ups (patients included and CEREDIH). CONCLUSIONS: A complete overview of immunoglobulin needs in PIDs is difficult to obtain. Supply tensions have been observed although PIDs are a priority indication. Measures must be proposed to ensure an adequate supply regardless of the location of patients in the territory.

[Chemistry approach for therapeutic education of children with hemophilia and their parents: Representation of complex phenomena related to treatment]. / La chimie au service de l'éducation thérapeutique des enfants atteints d'hémophilie et de leurs parents : représentation de phénomènes complexes liés au traitement.

INTRODUCTION: The therapeutic management of hemophilia is based on replacement therapy by clotting factor concentrates and may require several injections per week. In teenagers, non-compliance with treatment may be responsible for major orthopedic complications. The aim of this study was to develop and assess an educational intervention for children with hemophilia and their parents, thus illustrating the complex phenomena related to treatment and its adhesion. METHODS: The construction of the educational workshop and tools was based on the concrete, visual, and playful representation of the following concepts: pathophysiology, the replacement therapy's mechanism of action, drug elimination requiring repeated administrations, and inhibitor development. The procedure was then assessed by a sample of children and parents using a questionnaire. RESULTS: A 60- to 90-min workshop was developed. The different tools used to illustrate the severity of the disease, the effect of the injected drug, drug elimination, and the inhibitor effect were: a blue-to-transparent colorimetric scale in bottles, a weekly timeline, Muppets, and a slow redox reaction. Five children and eight parents assessed this educational intervention with a rating of 3.75/4 (±0.10) and 3.60/4 (±0.45), respectively. CONCLUSION: The intervention developed could be transposed to other chronic diseases with similar therapeutic characteristics (including replacement mechanism of action and pharmacokinetics). Understanding the transmitted pharmacological concepts in a playful way is a major challenge to encourage treatment adhesion during adolescence.

[Pharmacist's interventions on outpatient prescriptions in a university hospital drugs sales service]. / Interventions des pharmaciens sur les prescriptions ambulatoires dans le cadre de l'activité de rétrocession d'un centre hospitalier universitaire.

UNLABELLED: For public health reasons, some drugs are only available in hospital drugs sales service. This activity takes place in a specific risk context of organization, patients and/or drugs. A systematic prescription analysis by pharmacist contributes to securise treatment dispensed. The aim of this paper is to present the main drugs problems in the analysis of outpatient prescriptions and pharmaceutical interventions in three units of hospital drugs sales service belong to university hospital. METHODS: Throughout the year 2013, drug problems detected were recorded prospectively and systematically. RESULTS: Of the 22,279 prescriptions analyzed, 247 pharmaceutical interventions (1.1%) were detected including 27.6% of problems concerning the dosages, 15.4% the unconformity, 6.9% contraindications. Regarding ATC drugs classes, we found 43.7% for anti-infectives and 17.4% for antineoplatics. The overall acceptance rate is 81.8%. CONCLUSION: These results show the importance of the analysis of outpatient prescriptions before dispensing and the need to have all prescriptions, clinical and biological elements and to develop interprofessionality. The implementation of a platform for dematerialized data exchanges between professionals, including data from the pharmaceutical patient record should contribute to improving drug management of the patient.

Seventy-two total knee arthroplasties performed in patients with haemophilia using continuous infusion.

BACKGROUND AND OBJECTIVES: Total knee replacement (TKR) is the treatment of choice in case of end-stage knee arthropathy, the main complication of haemophilia. We report here a retrospective evaluation of 72 total knee replacement in 51 haemophilia A and B patients using continuous infusion of factor concentrates (CIFC). MATERIALS AND METHODS: Patients were evaluated on the basis of the following efficacy and safety criteria: range of motion, surgery-related blood loss by three different methods, factor consumption and occurrence of short and long term complications. RESULTS: Kaplan-Meier analysis showed a removal-free survival of TKRs of 88.4% 10years after surgery. Most patients were satisfied with their prosthesis and described pain relief and improved mobility and better quality of life after surgery. The long term follow-up showed a mean range of motion at 86° with a flexion deformity of 4°. The blood loss differed significantly according to the method used for measurement. No life-threatening bleeding occurred. Twenty six haematomas (36.1%) and 2 haemarthroses (2.7%) occurred in 38.8% of cases during the first three postoperative weeks, with no significant impact on the orthopaedic outcome. The average factor consumption during hospitalization was 79IU/kg/day for patients with haemophilia A and 99IU/kg/day for patients with haemophilia B. Infections occurred in 4.1% of patients. One patient with severe haemophilia A developed an inhibitor. CONCLUSIONS: The multidisciplinary approach and the homogeneous management of our large cohort allowed the achievement of excellent functional results. Our results confirmed previously reported data on the safety and efficacy of CIFC in situations requiring intensive factor replacement, such as TKR surgery.

[Management of bradykinin-mediated angioedema]. / Prise en charge en urgence de l'angiœdème à bradykinine.

OBJECTIVES: Present the clinical signs of bradykinin-mediated angioedema, a disease little known to intensive care anaesthesiologists, and develop their scientific basis with recent data on management in emergency and perioperative care. DATA SOURCES: International recommendations and recent general reviews. Data collection was performed using the Medline database with the keyword: angioedema. STUDY SELECTION AND DATA EXTRACTION: Research studies published during the last 10 years were reviewed. Relevant clinical information was extracted and discussed. DATA SYNTHESIS: Angioedema is a clinical syndrome characterized by episodes of transitory recurrent submucosal and subcutaneous oedema, called attacks. During an attack, the oedema may be localized at the level of the skin and/or ENT and digestive tract mucosa. This syndrome is not due to an allergic reaction. It is related to a C1 complement inhibitor deficiency or an increase in factor XII resulting in the excessive release of bradykinin, which leads to capillary permeability. There are hereditary and acquired forms, notably associated with the use of ACE inhibitors and sartans. This rare disease should be recognized by anaesthesiologists and intensive care and emergency physicians because, in the absence of specific treatment, it can be life-threatening due to the appearance of laryngeal oedema. In addition, there is a risk that the patient may have an attack during the perioperatory period, due to surgical trauma. International recommendations exist, and there are new molecules available in France. For moderate attacks, treatment is based on tranexamic acid. For hereditary forms, according to the localization and gravity of the attacks, emergency treatment is based on the use of Icatibant, a bradykinin B2 receptor inhibitor, and C1 inhibitor concentrate. For pregnant women and acquired forms, C1 inhibitor concentrate is the treatment of reference. Antalgic and perfusion treatments should not be neglected, and should be modified as a function of clinical signs. High-risk situations (perioperatory period, birthing, dental care) should be identified and short-term prophylaxis put in place before any procedure that may trigger an attack. Algorithms are proposed for the diagnosis, treatment and prevention of attacks. Recommendations exist for during childbirth, in which case C1 inhibitor concentrate should be used. CONCLUSION: Bradykinin-mediated angioedema should be evoked in the case of recurrent and transitory oedema. Emergency management has evolved thanks to the commercialization of new molecules. Prevention of attacks during surgery and for during childbirth is important. The availability of C1 inhibitor concentrate in sufficient doses should be verified prior to the procedure. A multi-site reference centre (CREAK) has been created to help clinicians manage this disease. Patients with this disease should be identified in emergency departments. Health establishments, which cannot all have emergency stocks, should set up procedures for rapid provision or the transfer of patients to reference sites.

[Management of a scabies epidemic in the Strasbourg teaching hospital, France]. / Gestion d'une épidémie de gale aux Hôpitaux universitaires de Strasbourg.

CONTEXT: An outbreak of scabies occurred in the geriatric department of the Strasbourg University Hospital in September 2005. The index case presented with hyperkeratosic scabies, an extremely contagious form. The epidemic spread to several wards and pavilions and also contaminated healthcare staff and patient's families. OBJECTIVE: Our objective was to describe the outbreak, its progression, and the measures taken to eradicate it. METHODOLOGY: All healthcare workers, patients, and families affected in the outbreak were retrospectively studied, using medical prescriptions recorded by the hospital pharmacy, listings established by the occupational health department, and patient files. RESULTS: Two epidemic waves were recorded, between August 31 and December 16, 2005, affecting 51 patients and staff members in the geriatric department, with a total of 58 episodes of scabies, seven of which were recurrences. Three main measures were taken to eradicate the epidemic: setting up of "contact" isolation precautions, information for the affected individuals, and treatment of the infected patients associated to mass treatment of contact cases. The mass treatment was widely applied, involving 490 patients and 592 caregivers. All of these measures successfully curtailed the outbreak in 3 months. CONCLUSION: Rapid and radical action is essential to prevent extension of scabies within a community.

[Best practice agreement: implementation of best practice guidelines in HCL hospitals in Lyon, France]. / Contrat de bon usage : mise en oeuvre opérationnelle des référentiels de bon usage aux hospices civils de Lyon.

Since 2004, the Hospices Civils de Lyon (HCL) hospitals are committed to comply with best practice guidelines for healthcare products that are reimbursed in addition to diagnosis related groups' (DRGs) tariffs in France, and that, even before the publication of the law concerning best practice agreement. It has been necessary to adapt national drugs best practice guidelines to every-day practice. A working group, COPIL RBU, has been created in HCL hospitals to manage the best practice guidelines locally. This group has two main activities: it conducts a scientific and regulatory information watch and follows up emerging indications at HCL. The group's best practice guidelines contain a classification of indications into three categories: approved indications (market authorization and temporary protocol of treatment), currently-assessed indications and contra-indications. Our best practice guidelines are more than a rewriting of national guidelines since they include emerging indications validated by prescribing physicians at HCL hospitals. A scientific argumentation is made for each emerging indication that is classified in our guidelines, based on the level of scientific evidence available. The practical use of our best practice guidelines is made through a best practice prescription that enables the traceability of drugs from the prescription to the administration to the patient. These prescriptions are accompanied with best practice guidelines made by medical and pharmaceutical professional groups. Audits will then be conducted to assess the indications' conformity to our guidelines and to have a better knowledge of current medical practice.

[Off label use of recombinant activated factor VII: a practice survey]. / Le facteur VII activé recombinant hors Autorisation de mise sur le marché à l'heure de la tarification à l'activité: enquête de pratique.

OBJECTIVES: To evaluate the impact of local recommendations on off label use of recombinant activated factor VII. TYPE OF STUDY: Observational, retrospective. MATERIAL AND METHODS: Recommendations have been diffused by a local working group in 2004, concerning seven groups of indications (traumatology, cardiac, hepatic and various surgeries, obstetrics, neurology and haematology). Conformity to recommendations was studied according to 4 axes: respect of prescribing procedure, indication, posology, and pre ones required with the administration. RESULTS: There were thirty-one uses from 2004 to 2006. Thirty patients presented a massive haemorrhage (blood products before administration of recombinant activated factor VII expressed in median [min-max]: red blood cell unit=15 [0-37], fresh frozen plasma=11 [0-21]). Gravity score at the admission: SAPSII=55+/-22 (average+/-SD), 87% patients presented haemorrhagic shock. Prescribing procedure was in conformity with recommendations in 45%, indications were correct in 74%, posology in 55%, and 16% of prescriptions were completely conform. CONCLUSION: With the tariffing to the activity reform, the reimbursement of off label use of expensive molecules will depend on the respect of the evidence-based medicine. According to this study, the observance of local recommendations was insufficient. Rationalizing prescriptions for practice improvement seemed to be difficult and challenging.

The pharmacokinetics of coagulation factors.

In this article, we provide a summary of the generally accepted approaches to the design and analysis of studies examining the pharmacokinetic (PK) profile of an infused coagulation factor in patients with a deficiency of one or more of these factors. Furthermore, we briefly review the known PK results for various commercially available coagulation factor preparations under single and continuous infusion.

Major surgery in a severe haemophilia A patient with high titre inhibitor: use of the thrombin generation test in the therapeutic decision.

Summary. In haemophilia patients with inhibitor, elective orthopaedic surgery is usually performed under recombinant activated factor VII (rFVIIa). We report here the case of a severe haemophilia A patient with a high inhibitor who needed a bilateral total knee arthroplasty. Recombinant FVIIa was previously shown to be ineffective for the treatment of muscle and joint bleedings, and he had a history of excessive postoperative bleeding under activated prothrombin complex concentrate (APCC). Thrombin generation test (TGT) was used to assess the efficacy of Factor Eight Inhibitor Bypassing Activity (FEIBA). Insufficient correction of thrombin-generating capacity was observed after administration of 75 U kg(-1) FEIBA. In a multidisciplinary environment, a bilateral total knee arthroplasty was performed using a protocol combining immunoadsorption of inhibitors preoperatively associated with FVIII replacement during a first phase followed by FEIBA when the inhibitor reappeared. To our knowledge this is the first direct application of TGT in the management of haemophilia patients with inhibitor, which indicated that a sequential use of immunoadsorption, FVIII and FEIBA was the most appropriate treatment to perform this major elective surgery. This case demonstrates that this combined protocol can be safely used to cover major surgery in inhibitor patients. In addition, it also suggests that TGT may have a major contribution in the decision-making process of the most adapted therapy for the treatment of such high-risk patients.

[The circulation of anesthetic agents at Edouard-Herriot Hospital]. / Le circuit du médicament en anesthésie à l'hôpital Edouard-Herriot.

In order to improve quality, practice evaluation is a major tool for hospital management. For many years anaesthesia has been monitored by some form of quality assurance programme. However, despite the improvement in anaesthetic techniques, major problems persist, particularly with the use of anaesthetic agents. Drug administration is the first cause for malpractice and death in anaesthesia. The aim of this study was to analyse drug circuits in anaesthesia, with special reference to French regulations. In 13 theatres, doctors and nurse anaesthetists were interviewed by a pharmacist with a focus on following items: prescription, preparation, administration, management, storage, conservation, information, and regulations. Results demonstrated that practice organisation and information transfers were mainly by oral route. The low proportion of written information, especially for preoperative prescription, did not comply with regulations. Nurse anaesthetists were the main actors in drug handling. Common practice patterns throughout the hospital were non existing. In each theatre, a storage of usual drugs for four weeks was found, whereas in pharmacies drugs were stocked for a 2-week period only. Standardised and written procedures, as well as pharmaceutical practice guidelines, are essential for decreasing the risk and improving quality. Such a procedure requires the full participation of anaesthetists and nurses.

[Sleepiness and sleep apnea syndrome. Analysis of 188 questionnaires (102 patients and 86 controls)]. / Somnolence et syndrome d'apnées du sommeil. Analyse de 188 questionnaires (102 malades et 86 témoins).

A questionnaire was given to 102 obstructive sleep apnea patients and 86 controls. A somnolence index was defined by averaging the scores of the answers to eleven questions concerning sleepiness. This index separated patients and controls (P < 0.0001). It was correlated with the apnea + hypopnea index (r = 0.32, P < 0.001), the body mass index (r = 0.45, P < 0.001) and with an objective measurement of sleepiness obtained from a modified multiple sleep latency test (r = -0.54, P < 0.001). Depending upon the current occupation, the tendency to fall asleep decreased in the following order: watching TV, passenger in a means of transport, reading, attending a show, attending a meeting, driving a car, and eating. This order is the same in patients and controls, irrespective of their "overall sleepiness". Thus, the circumstances of falling asleep are indicative of the severity of sleepiness.

Nocturnal pollakiuria is a symptom of obstructive sleep apnea.

An increased urine excretion has been reported in obstructive sleep apnea (OSA) patients, but it is not clear whether it results in an increased number of nocturnal micturitions. The present study was aimed at investigating the frequency of nocturnal micturitions in OSA patients using a standardized questionnaire prospectively given to 102 OSA patients and 86 healthy male subjects. The frequency of nocturnal micturitions was significantly greater in the OSA patients than in the healthy subjects (more than 70% of the OSA patients with an apnea+hypopnea index > 50 reported nocturnal micturitions more than twice a week versus less than 25% of the healthy subjects, p < 0.0001). The number of nocturnal micturitions was also greater in the OSA patients than in the healthy subjects. There was an effect of age on the frequency of nocturnal micturitions; however, when age-matched subsamples were considered, there was still a significant difference between OSA patients and healthy subjects. In a subgroup of 25 OSA patients reevaluated after at least 1 year of home treatment with nasal continuous positive airway pressure the reported frequency of nocturnal micturitions had significantly decreased (p < 0.001). These results suggest that investigations aimed at establishing a diagnosis of OSA should be part of the work-up of patients complaining of nocturnal pollakiuria.