Anaphylactic reactions to local anesthetics in dental practice: a nationwide French retrospective study.

OBJECTIVES: The primary aims of the present study were (1) to quantify and characterize anaphylactic type I reactions related to local anesthetics (LAs) drawing on the French Pharmacovigilance Database System over a 35-year period and (2) to focuse on reactions associated with dental procedures. The secondary aim was to infer an incidence rate in dental practice. MATERIALS AND METHODS: All cases of anaphylactic reactions were selected using the algorithmic Standardized MeDRA Query "anaphylactic reaction." For each reaction, comprehensive data were collected, in particular the severity of symptoms, risk factors for anaphylaxis, and allergy testing. Imputability was assessed and a crude incidence rate in dental practice was estimated. RESULTS: The first-line search identified 416 anaphylactic reactions, mostly of grade II (138) or III (240) severity. When restricted to dental practice, this number fell to 26 (grade I: 4; grade II: 10; grade III: 11; and grade IV: 1). Lidocaine was most often involved (81.49%) and mostly associated with anaphylactic reactions of grade II and III. Overall, 11 cases of fatal anaphylaxis were recorded, but no in dental practice. In dental practice, lidocaine was also the most frequently involved LA (57.69%). CONCLUSIONS: All these findings highlight the very low incidence of type I-IgE-mediated reactions to LA, particularly in dental practice. The incidence rate of LA anaphylctic episodes in dental practice was estimated as 0.0261 anaphylactic episodes per million LA cartridges. CLINICAL RELEVANCE: True anaphylactic reactions to LAs do occur and may justify a thorough investigation in dental practice.

Fatal and life-threatening ADRs associated with paliperidone palmitate: an observational study in the French pharmacovigilance database.

INTRODUCTION: Paliperidone palmitate (PP), a long-acting intramuscular formulation of paliperidone, has been marketed in Europe within the last 10 years and provides an important treatment option for patients with schizophrenia.Our aim was to describe PP-related adverse drug reactions (ADRs) leading to death or life-threatening events, specifying their main clinical and pharmacological characteristics. METHODS: This observational study was a retrospective review of PP-related ADRs in the French pharmacovigilance database between January 1, 2013, and December 31, 2019. RESULTS: Out of 473 PP-related ADRs, we identified 13 deaths and 14 life-threatening events. ADRs were primarily cardiorespiratory (n = 17; 63%). Other symptoms observed were mainly metabolic (n = 4), digestive (n = 4), and neurological (n = 4). Cardiorespiratory symptoms were generally observed within first 6 months after initiation of treatment (11 out of 17 cases), unlike metabolic disorders (all 4 cases 12-21 months after initiation). Cardiac arrests and sudden unexpected deaths occurred 10-14 days after the last PP once-monthly injection (23 cases) or 11-24 days after the last PP three-monthly injection (remaining 4 cases). No PP blood concentration assays were performed for these patients. DISCUSSION: In this study, PP-related ADRs leading to death or life-threatening events mainly presented with cardiorespiratory symptoms and tended to occur in the first 6 months after the initiation of treatment and within postadministration periods aligned with peak plasma PP concentrations. The hypothesis of supratherapeutic drug concentrations following intramuscular PP injection must be raised. CONCLUSION: PP-related ADRs leading to death or life-threatening events mainly presented with cardiorespiratory symptoms. Cardiac arrests and sudden unexpected deaths following initiation of PP treatment could be due to supratherapeutic drug concentrations. This study highlights the need to monitor blood concentrations of PP.Key pointsAdverse reactions to paliperidone palmitate can lead to death or life-threatening events.It is hypothesized that cardiac arrests and sudden unexpected deaths following initiation of paliperidone palmitate treatment could be due to supratherapeutic drug concentrations.This paper proposes the need to monitor blood concentrations of paliperidone palmitate in future studies.

Ibrutinib, a Bruton's tyrosine kinase inhibitor, a new risk factor for cryptococcosis.

PURPOSE: Invasive fungal diseases and especially Cryptococcus neoformans infections are increasingly reported in patients with hematological malignancies receiving ibrutinib, a Bruton's tyrosine kinase inhibitor. PATIENTS AND METHOD: We reported three additional cases and reviewed 16 previous published cases together with cases from the international pharmacovigilance database. RESULTS: Patients were mainly treated for chronic lymphocytic leukemia. Cryptococcosis mostly occurred during the first six months (66%) and especially the first two months (44%) of treatment. Clinical presentation is often pulmonary (68%) and the outcome is usually favorable despite ibrutinib continuation. CONCLUSION: Clinicians must be aware of this infection in patients with hematological malignancies on ibrutinib.

Antibiotic prophylaxis for the prevention of infective endocarditis for dental procedures is not associated with fatal adverse drug reactions in France.

BACKGROUND: One of the major reasons to stop antibiotic prophylaxis (AP) to prevent infective endocarditis (IE) in the United Kingdom but not in the rest of the world was that it would result in more deaths from fatal adverse drug reactions (ADRs) than the number of IE deaths. The main aim of this study was to quantify and describe the ADRs with amoxicillin or clindamycin for IE AP. The second aim was to infer a crude incidence of anaphylaxis associated with amoxicillin for IE AP. STUDY DESIGN: The Medical Dictionary for Regulatory Activities (MedDRA) was used to group ADRs for IE AP using the broad Standardized MedDRA Queries "Anaphylactic reaction, Amoxicillin, Clindamycin, Clostridium Difficile infection" to the French Pharmacovigilance Database System. From this first-line collection, we selected all cases occurring for IE AP and ultimately, the cases for IE AP for a dental procedure. Then, each case was analyzed. RESULTS: Of 11639 first-line recorded ADRs, 100 were for IE AP but no fatal anaphylaxis to amoxicillin or clindamycin and no C. difficile infection associated with clindamycin were identified. Only 17 cases of anaphylaxis to amoxicillin related to dental procedures were highlighted. The estimation of the crude incidence rate of anaphylaxis associated with amoxicillin for IE AP for invasive dental procedure was 1/57 000 (95% CI 0.2-0.6). CONCLUSIONS: Fatal or severe ADRs with amoxicillin or clindamycin is not a rational argument to stop IE AP before invasive dental procedures.

[Oral anticoagulants adherence in elderly patients treated for atrial fibrillation in the era of direct oral anticoagulants]. / Observance du traitement anticoagulant oral chez le sujet âgé à l'ère des anticoagulants oraux directs.

BACKGROUND: The aim of this study was to determine the level of adherence to oral anticoagulants in the population of elderly patients treated for a non-valvular atrial fibrillation (AF) in the era of direct oral anticoagulants. PATIENTS AND METHOD: This transversal study used Morisky scale to assess adherence to oral anticoagulants. We also collected patients' reviews about the treatment and factors explaining a poor adherence. RESULTS: Between January and June 2015, 64 patients were included in Loire Atlantique. Average age was 77.8 years, CHA2DS2-VASc score was 4.06 and treatment (vitamin K antagonists [VKAs] in 78% patients) was prescribed since 4.3 years. According to Morisky scale, 84.4% of patients had a good adherence. There was 88% of good adherence with AVK versus 71% with direct oral anticoagulant, there was no statistically significant difference. The prescriber and the knowledge of anticoagulant treatment role seemed to be determinant factors. CONCLUSIONS: The level of adherence for oral anticoagulant appears higher than in most published studies. Diversification of therapeutic options could constitute an aid to personalize the prescription in order to improve it.

[Intensity modulation in breast radiotherapy: development of an innovative field-in-field technique at Institut Gustave-Roussy]. / Modulation d'intensité en radiothérapie mammaire : développement d'une méthode innovante de champ dans le champ à l'institut Gustave-Roussy.

PURPOSE: To assess the potential dosimetric gain of presegmentation modulated radiotherapy (OAPS, DosiSoft™) of breast, compared to routine 3D conformal radiotherapy. PATIENTS AND METHODS: Twenty patients treated with conservative surgery for breast cancer (9 right and 11 left sided) with various breast volume (median 537 cm(3); range [100-1049 cm(3)]) have been selected. For each patient, we have delineated a breast volume and a compensation volume (target volumes), as well as organs at risk (lungs and heart). Two treatment plans have been generated: one using the routine 3D conformal technique and the other with the presegmentation algorithm of DosiSoft™ (OAPS). The dose distribution were analyzed using the conformity index for target volumes, mean dose and V30 Gy for the heart, and mean dose, V20 Gy and V30 Gy for lungs. RESULTS: Over the 20 patients, the conformity index increased from 0.897 with routine technique to 0.978 with OAPS (P<0,0001). For heart and lung, OAPS decreased irradiation (mean cardiac dose 1,3 vs 1,6 Gy [P<0,0001] and pulmonary V20 Gy 6,6 vs 7,1 [P<0,0001]). CONCLUSION: OAPS (DosiSoft™) is an original method of segmentation of breast. It is automatic, fast and easy, and is able to increase the conformity index, while sparing organ at risk.

[Epidemiologic study of urinary calculi in Western France]. / Etude épidémiologique des calculs urinaires dans l'Ouest de la France.

OBJECTIVES: An epidemiologic study of urinary calculi (N = 1843) was conducted in Western France: distribution according to the main chemical compounds, age and sex. Comparison with the results of a study with national recruitment (N = 10,617) and a study with regional recruitment (N = 1774). METHOD: The study involved 1843 stones characterized beforehand by morphological analysis associated with infra-red spectrophotometry (FTIR). If analysis of the composition of the stones was carried out on the totality of calculi, studies related to age and sex included only 1583 cases. Comparison of percentages was made using chi 2 test. RESULTS: The composition in main compounds of calculi was comparable with the results of other studies; minor significant compounds presented great differences, raising the problem of interpretation of the infra-red spectra of the latter. Hence, our work was directed towards the analysis of the major compounds and we showed, like most authors, that monohydrate calcium oxalate is predominant in male (46%) as well as in females (37%). Calculi average sex-ratio was 2.19 but dehydrated calcium oxalate sex-ratio was 4.42, suggesting that this compound is found mainly in men. Conversely, for the majority of phosphate stones, the sex-ratio was lower or equal to one, indicating that they predominate in women. Infectious calculi (particularly struvite calculi) appeared slightly more frequent in our population than in other studies, whereas the number of uric acid calculi was lower. This, however, remains to be confirmed. CONCLUSION: The population studied was not significantly different from the national population regarding lithiasis, except perhaps for uric acid and struvite calculi, despite specific regional differences in diet and the role of nutritional factors in lithogenesis.

Autologous skin banking.

Small amounts of excess autograft are commonly harvested during burn procedures, and typically these are discarded. However, the resources of a local skin bank may be used to preserve this tissue for a later autologous use. This has been a routine practice in our institution and we feel that it has impacted favorably on patient care. In this paper we report 42 consecutive applications of autologous frozen skin and illustrate the technique with a case report.

Total body irradiation and high-dose cyclophosphamide, BCNU and VP-16 (CBV) as a new preparatory regimen for allogeneic bone marrow transplantation in patients with advanced hematologic malignancies.

To increase the cure rate of advanced hematologic malignancies following allogeneic bone marrow transplantation we sequentially evaluated two intensified conditioning regimens. Eleven patients with acute myeloblastic leukemia (AML) beyond the first complete remission or chronic myelogenous leukemia (CML) not in first chronic phase received an association of 13.5 Gy of fractionated total body irradiation (TBI) followed by cyclophosphamide (CY) 120 mg/kg. Following this regimen, the probability of relapse was 47% at 3 years and the non-relapse mortality rate was 27%. Given the acceptable tolerance of this regimen, 13.5 Gy fractionated TBI was associated with intensified chemotherapy consisting of a combination of CY 120 mg/kg, carmustine 300 mg/m2 and etoposide 600 mg/m2 (CBV). This regimen was administered to 22 patients with comparable diseases. Of these patients, 7 received a transplant from a matched unrelated donor and 2 other patients received a second transplant from the original genoidentical donor. For 15 patients with a genoidentical donor, including the 2 second transplant, the 3 year probability of survival, disease-free survival and relapse are 40%, 40% and 14%, respectively. No regimen-related toxic deaths were recorded during the first 100 days. Of 7 patients with matched unrelated donors, 3 died before day 100, one death being directly attributable to the regimen. Early non-fatal regimen-related toxicity consisted mainly in grade II mucositis with no grade III or IV toxicity in recipients of genoidentical marrow. The late deaths were mainly due to chronic GVH-related complications. In conclusion, the association of fractionated 13.5 Gy TBI and CBV carries a high antileukemic activity and an acceptable toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Detection of hepatitis B viral DNA by polymerase chain reaction in dialysis patients.

The polymerase chain reaction (PCR) was used to search for hepatitis B virus (HBV) DNA sequences in the sera of 51 dialyzed patients (26 women, 25 men; mean age 60.5 years, range 35 to 85). Two different sets of specific primers for HBV core and surface gene sequences were synthesized and used for each sample. Controls were 90 HBV negative blood donors. Results were analyzed according to other serological markers of HBV. Among the eight HBsAg positive patients (anti-HBc+: 8/8), seven were positive for HBV DNA. Four of eight patients were vaccinated but later developed acute HBs hepatitis. The presence of HBV DNA was detected in six of 43 HBsAg negative patients (anti-HBc+: 5/6; anti-HBs+: 3 of 6; HBeAg: 0 of 6; anti-HBe: 2 of 6). These six patients were vaccinated and four of six developed mild and transient cytolytic hepatitis (3 before vaccination; 2 later). These results showed that HBsAg seronegative patients can be infectious. The role of HBV vaccination and/or the existence of variations in the structure of the viral genome is discussed.

[Results of dietary evaluation during calcium oxalate and calcium phosphate lithiasis]. / Résultats du bilan alimentaire au cours de la lithiase oxalo-phospho-calcique.

In order to better understand the role of diet in etiology of urolithiasis, 84 oxalo-phospho-calcic-lithiasic patients (52 men, 32 women) have been studied by a nutritional week-interview and by urinary and blood testing. Diet data were compared to an ideal standard. Total caloric intake was 2428 +/- 651 calories/d; this intake is high in 7% women and 40% men. 79% out of patients are fat. Protidic intake is 87 +/- 21 g/d higher than 1 g/kg/d in 84.5% of patients. Lipids are high in 38.9 +/- 7%, glucid are low in 45.3 +/- 7%. Calcium intake is 934 +/- 406 mg/d, sodium intake is 12.9 + 3 g/d. Water intake is 2305 +/- 759 ml/d. Different groups of patients are studied: a) 21 patients with mean age of 43 +/- 12 years have recurrent lithiasis (R). This group is compared to 48 patients with 37 +/- 44 years who have a single lithiasis. Half of (R) patients have hypercalciuria, hyperphosphaturia and hyperoxaluria. Diet study is no different between these two groups. b) Other groups are studied: 21 have hyperophosphaturia (HPU) without hypophosphoremia and they have hypercalciuria, hyperuraturia and high urinary urea; diet shows higher glucicid and potassium intake than group with normal phosphaturia; 23 have hypercalciuria (HCU) and high uraturia and phosphaturia: diet study shows no difference with a group with normal calciuria. 21 have hyperoxaluria (HOU): diet study of a normal oxaluric group shows higher lipid intake, lower glucidic and calcium intake; 22 have hyperuraturia (HAU) and higher urinary urea, sodium and potassium than normouraturia group: in this group potassium intake is higher.(ABSTRACT TRUNCATED AT 250 WORDS)

[Adrenal myelolipoma and Castleman's pseudotumor. A case of association in a retroperitoneal tumor]. / Myélolipome de la surrénale et pseudo-tumeur de Castleman. Un cas d'association au sein d'une tumeur rétropéritonéale.

The authors report a case of a voluminous retroperitoneal tumor as an incidental finding in a patient with acute urine retention induced by an ovarian compressive cyst. Radiological findings supported the hypothesis of a malignant tumor. The histological examination of the surgical specimen only permitted the diagnosis and showed the association of an adrenal myelolipoma with a Castleman's pseudo-tumor.

[Evolution of motor nerve conduction and Hoffmann reflex in 100 patients with chronic renal failure treated by periodic hemodialysis (author's transl)]. / Evolution de la vitesse de conduction nerveuse motrice et du réflexe d'Hoffmann chez cent dialysés chroniques.

The study of motor nerve conduction (MNC) and H. reflex was carried out on 100 chronic uraemic patients, fifty-four males and fourty-six females, treated by periodic hemodialysis. The MNCV is more frequently normal in females than in males. Periodic hemodialysis improves MNCV but sometimes uraemic neuropathy appears with hemodialysis. The MNCV is oftener improved than H. reflex latency. Results are neither significantly improved by a greater number of hemodialysis seances nor in function of the different dialyzers. Any kidney activity does not modify the nerve conduction.

[Postoperative peritonitis. Use of metabolic disorders as criteria for reoperations]. / Les péritonites post-opératoires. Utilisation des perturbations métaboliques comme critères de réintervention

The authors compared three groups of subjects: - the first group (11 patients) : re-operated for post-operative peritonitis; - the second group (6 patients) : re-operated for evisceration without any underlying lesion; - the third group (8 patients) : non-reoperated, complicated abdominal surgery. Study of the different laboratory parameters helped to identify a number of changes which could plead in favor of reintervention, in the group of peritonitis. Among these modifications, the progressive fall in the urinary Na/K ratio and the negativity of the nitrogen balance appear to play a privileged role.