Prescription opioid analgesic use in France: Trends and impact on morbidity-mortality.

BACKGROUND: While data from USA and Canada demonstrate an opioid overdose epidemic, very little nation-wide European studies have been published on this topical subject. METHODS: Using a nationally representative sample of the French Claims database (>700,000 patients), the exhaustive nationwide hospital discharge database, and national mortality registry, all patients dispensed at least one prescription opioid (PO) in 2004-2017 were identified, to describe trends in PO analgesic use, shopping behaviour, opioid-related hospitalizations and deaths. Annual prevalence of PO use and shopping behaviour (≥1 day of overlapping prescriptions from ≥2 prescribers, dispensed by ≥3 pharmacies) was estimated. RESULTS: In 2004-2017, the annual prevalence of weak opioid use codeine, tramadol and opium rose by 150%, 123%, and 244%, respectively (p < 0.05). Strong opioid use increased from 0.54% to 1.1% (+104%, p < 0.05), significantly for oxycodone (+1950%). Strong opioid use in chronic noncancer pain rose by 88% (p < 0.05) and 1180% for oxycodone. Opioid shopping increased from 0.50% to 0.67% (+34%, p < 0.05), associated with higher mortality risk HR = 2.8 [95% confidence interval (CI): 1.2-6.4]. Opioid-related hospitalizations increased from 15 to 40 per 1,000,000 population (+167%, 2000-2017), and opioid-related deaths from 1.3 to 3.2 per 1,000,000 population (+146%, 2000-2015). CONCLUSIONS: This study provided a first European approach to a nationwide estimation with complete access to several national registries. In 2004-2017 in France, PO use excluding dextropropoxyphene more than doubled. The increase in oxycodone and fentanyl use, and nontrivial increasing trend in opioid-related morbidity-mortality should prompt authorities to closely monitor PO consumption in order to prevent alarming increases in opioid-related morbidity-mortality. SIGNIFICANCE: In 2004-2017, prescription opioid use in France at least doubled and oxycodone use increased particularly, associated with a nontrivial increase in opioid-related morbidity-mortality. Although giving no indication for an 'opioid epidemic,' these findings call for proper monitoring of opioid use.

Spontaneous rupture of Achilles tendon and Cushing's disease. Case report.

Spontaneous rupture of Achilles tendon is observed in patients with tumors, metabolic disorders, infections and systemic diseases. Fluoroquinolones may cause tendinopathies. In addition, spontaneous rupture uncommonly occurs in Cushing's syndrome. We report a case of Cushing's disease revealed by recurrent rupture of Achilles tendon. Tendon tears are described in patients receiving long-term steroid treatment, probably via a mechanism similar to that one occurring in Cushing's syndrome. Although exceptional, this diagnosis should be discussed in patients with spontaneous rupture of Achilles tendon.

Double-blind randomized evaluation of clinical and biological tolerance of polyethylene glycol 4000 versus lactulose in constipated children.

OBJECTIVES: To assess the safety of a polyethylene glycol (PEG) 4000 laxative without additional salts in pediatric patients. STUDY DESIGN: This was a 3-month multicenter, randomized, double-blind, double-dummy, lactulose-controlled, parallel study enrolling 96 ambulatory constipated children aged 6 months to 3 years, treated daily with 4-8 g PEG or 3.33 g-6.66 g lactulose. Total protein, albumin, iron, electrolytes, and vitamins B9 (folates), A and D (25OHD3) were measured in blood before and after treatment (day 84) in a central laboratory. RESULTS: The percentage of children with at least one value out of normal range at day 84 with respect to baseline status (with or without at least one value out of normal range), i.e. the primary endpoint, was 87% and 90% in the PEG and lactulose groups, respectively, without any difference between groups. The whole blood parameters showed no qualitative or quantitative treatment-related changes. Vitamin A values were above normal range in 56% and 41% of children at baseline versus 33% and 36% at day 84 in the PEG and lactulose groups, respectively. Iron values were similarly under normal range in 47% and 51% at baseline versus 42% and 51% at day 84. Clinical tolerance was similar for both treatments except for vomiting and flatulence, which were significantly higher with lactulose. Significantly higher improvements were evidenced with PEG regarding stool consistency, appetite, fecaloma and use of additional laxatives. CONCLUSION: This 3-month study in 96 constipated children aged 6 months to 3 years confirms the long-term tolerance of PEG 4000 in pediatrics and indicates a PEG efficacy similar to or greater than that of lactulose.

[Medico-economic study of percutaneous and surgical closure of ostium secundum type interatrial communications]. / Etude médico-économique de la fermeture percutanée et chirurgicale des communications interauriculaires de type ostium secundum.

The aim of this study was the medico-economic evaluation of the closure of ostium secundum type interatrial communications in 32 patients, treated by cardiac catheterisation (group A: n = 17) or by surgery (group B: n = 15). The success rate was 100% with the 2 techniques. With national cost scale data we evaluated the overall cost of the 2 treatments using the information system medical program, starting from homogenous groups of patients: 150 catheterisation, 169 and 170 surgery. As the value for the homogenous group of 150 patients was much lower than the price of the material used for catheterisation, an adjusted group of 150 patients including the price of this material was created. An evaluation in terms of an artificial index of activity was also performed. The average duration of hospital stay for group A was reduced by 6.1 days compared to group B (p < 0.001). The overall cost was lower in group A than in group B (p < 0.001), using the real and "adjusted" homogenous group of 150 patients, with a respective reduction of 7,582 Euros and 3,731 Euros. Surgery and catheterisation scored 8,167 points (17,756 Euros) and 2,726 points (5,926 Euros) per patient respectively on the artificial activity index. In conclusion, catheterisation reduced the duration of hospital stay and brought an economic benefit for the Assurance Maladie compared to surgery. However, surgery is more profitable for the hospital than catheterisation because of the high cost of the prosthesis, which is not taken into account with a homogenous group of non-specific patients. This could hamper the development of this innovative technique in a hospital subjected to overall budgetary constraints.

EMLA versus nitrous oxide for venous cannulation in children.

We compared EMLA cream with nitrous oxide (N(2)O) for providing pain relief during venous cannulation in children. In a prospective, double-blinded, randomized study, 40 children, 6-11 yr, ASA status I or II, undergoing scheduled surgery received either EMLA cream and inhaled air and oxygen (Group EMLA) or a placebo cream and inhaled 70% N(2)O in oxygen (Group N(2)O) before venous cannulation. Pain was evaluated with a visual analog scale and the Objective Pain Scale. The ease of venous cannulation and the observer's assessment of its efficacy for preventing pain were assessed. Heart rate, blood pressure, respiratory rate, and oxygen saturation were compared before and after venous cannulation. Visual analog scale scores (4.4 +/- 7.5 vs 3.9 +/- 9.3 mm, P = 0.85), Objective Pain Scale scores (median 0 [0-6] vs 0 [0-1], P = 0.61), efficacy (median 0 [0-1] vs 0 [0-1], P = 0.59), and ease of venous cannulation (0 [0-2] vs 0 [0-1], P = 0.84) were not different between EMLA and N(2)O groups, respectively. There was no statistical difference between the groups for the physiologic variables. Minor side effects were significantly more common in the N(2)O group (11 of 20) than in the EMLA group (7 of 20) (P = 0.0248). We conclude that both techniques provided adequate pain relief during venous cannulation, as demonstrated by the low pain scores.

Variability in hemoglobin levels: clinical implications. Case study of the anemic patient.

A historical, prospective, multicenter, observational study was conducted on data from October 1996 to December 1997 to determine the impact of hemoglobin (Hb) variability on the interpretation of maintenance anemia management outcomes in hemodialysis patients. Trends in mean Hb levels were retrospectively analyzed to determine whether there were any differences between 1-month Hb averages versus 3- or 6-month rolling averages. Results showed that: (a) Hb measurements exhibit wide variability between patients and within patients, regardless of the assessment method used, and (b) it is difficult to maintain patients within the 1 g/dL Hb spread recommended by NKF-K/DOQI. The largest variations in Hb readings were observed in 1-month readings, while 6-month rolling averages exhibited the least variability. These data illustrate the importance of assessing long-term trends in laboratory data before making incremental or decremental modifications in the anemia prescription.

Trichosporon beigelii funguria in renal transplant recipients.

Trichosporon beigelii funguria in renal transplant recipients is usually benign and is seldom associated with invasive or deep-seated infections.

Group A Streptococcus carriage among close contacts of patients with invasive infections.

During the past few years, the incidence of invasive group A Streptococcus (GAS) infection has been increasing. However, there are presently no clear recommendations regarding antibiotic prophylaxis for close contacts of index patients. The aims of this study were 1) to determine the prevalence of carriage of the same GAS strain as the patient's among contacts of patients with invasive infections and 2) to assess the importance of exposure duration. From March 1995 to March 1996, the authors prospectively included in the study all patients with invasive GAS infection, as defined by the Working Group on Severe Streptococcal Infections, who came to Hôpital Maisonneuve-Rosemont in Montreal, Quebec, Canada. An epidemiologic investigation was systematically carried out for each index case. Contacts were divided into two groups: those who had spent 24 hours or more with the index patient during the week preceding the beginning of his or her illness and those who had spent 12-24 hours with the index patient during that week. Strains of GAS were examined by serotyping (proteins M and T and the presence or absence of the serum opacity factor) and by characterization of streptococcal pyrogenic exotoxins (exotoxins A, B, and C). One hundred and two contacts of 17 index cases with invasive GAS infection were systematically screened. Contacts were considered positive if they carried the same strain of the bacterium and the same streptococcal pyrogenic exotoxin as the index case. Among the contacts who had spent at least 24 hours per week with their respective index cases, 13 out of 48 (27%) were found to be harboring the same serotype of GAS as the index patient (95% confidence interval 14.5-39.5). By comparison, only one of the 54 contacts in the 12- to 24-hour group (1.8%) was found to be carrying the same strain of the bacterium (95% confidence interval 0-5.3). This difference between the two groups was statistically significant (p<0.001). The median age of the positive carriers (10 years) was significantly lower than the median age of the noncarriers (39 years) (p< or =0.0005). This study showed that close contacts who had spent 12-24 hours with the index patient were rarely colonized with GAS. If antibiotic prophylaxis against GAS is recommended, it should probably target contacts who spent at least 24 hours with an infected patient during the week preceding illness onset.

Trends in antibiotic resistance of staphylococci over an eight-year period: differences in the emergence of resistance between coagulase positive and coagulase-negative staphylococci.

The antimicrobial susceptibilities of 1058 Staphylococcus aureus and 2,163 coagulase-negative staphylococci (CNS) isolates obtained from clinical specimen between 1988 and 1995, were determined against 13 anti-staphylococcal antibiotics. During the study period the resistance of Staphylococcus aureus to ciprofloxacin, ceftazidime, and norfloxacin increased significantly by 7%, 4%, and 6%, respectively (p < or = 0.001). By comparison, the antibiotic resistance of CNS to ceftazidime, oxacillin, norfloxacin, ciprofloxacin, fusidic acid, and cefoxitin increased by 20%, 17%, 15%, 14%, 12% and 10%, respectively (p < or = 0.001). Invasive and noninvasive S. aureus had similar antibiotic resistance, whereas CNS invasive isolates were more resistant than noninvasive isolates to every antibiotics, except vancomycin and fusidic acid. These differences were significant (p < 0.001) for oxacillin, cefoxitin, and clindamycin. Our observations confirm that staphylococci and particularly CNS isolates show an important rate of increased resistance to the standard antimicrobials used for therapy, and that the rate of emergence of resistance differ considerably between coagulase-positive and coagulase-negative staphylococci.

[Clinical pilot study on repeated use of heparin, vancomycin, colimycine locked flush solution for central intravenous implanted catheter in oncology]. / Etude clinique pilote de l'utilisation repétée dune solution héparine, vancomycine, colimycine en verrouillage systématique des chambres implantables avec cathéter centeral en cancérologie.

With an anti-infectious and an antithrombotic prophylaxis aims, a locked flush solution including heparin and vancomycin, was used systematically for implantable venous access system for each patient, from january to april 1995. Since the 6th of april 1995, in order to widen the antibiotic spectrum on Gram negative bacteriae, we added colimycin at the flush solution. In 1995, 342 hospitalised patients held this type of venous access and received chemotherapy and/or radiochemotherapy for cancer. Two thousand six hundred thirty three manipulations were done, 575 with the first flush solution, 2058 with the second. During the year, 15 implantable access system (4.4%) were considered as infected, only 3 (0.9%) were removed, in the first period. THe infectious rate seemed to be stable, but the bacterial assessment to be modified between the two periods. The Gram negative bacterial infections seemed to decrease with colimycin addition (33% versus 50%). These results must be confirmed by a long term and/or randomized study.

Axonemal tubulin polyglycylation probed with two monoclonal antibodies: widespread evolutionary distribution, appearance during spermatozoan maturation and possible function in motility.

Two monoclonal antibodies, AXO 49 and TAP 952, probed with carboxy-terminal peptides from Paramecium axonemal tubulin and with polyglycylated synthetic peptides, are found to recognize differently tubulin polyglycylation, the most recently identified posttranslational modification discovered in Paramecium axonemal tubulin. With these antibodies, we show that tubulin polyglycylation is widely distributed in organisms ranging from ciliated protozoa to mammals; it arose early in the course of evolution, but seems to be absent in primitive protozoa such as the Euglenozoa. Tubulin polyglycylation is the last posttranslational modification which takes place in the course of Drosophila spermatogenesis and its occurrence corresponds to the end of spermatozoan maturation. An involvement of polyglycylated tubulin in axoneme motility is suggested since AXO 49 and TAP 952 specifically inhibit the reactivated motility of sea urchin spermatozoa.

A massive new posttranslational modification occurs on axonemal tubulin at the final step of spermatogenesis in Drosophila.

Using two antibodies raised against Paramecium axonemal tubulin, a monoclonal antibody, AXO 49 (Callen et al., Biol. Cell 81, 95-119 (1994)), and a polyclonal antibody, PAT (Cohen et al., Biol. Cell 44, 35-44 (1982)), which have been shown elsewhere to detect a new posttranslational modification of tubulin presumably corresponding to polyglycylation, we have analyzed the occurrence of this modification during spermatogenesis in Drosophila. Results obtained by immunofluorescence on cysts isolated by laceration of testes showed that the antibodies reacted on axonemal microtubules of several species within the genus. Observation of different stages of differentiation of D. obscura sperm cells indicated, first, that the epitopes reactive with both antibodies appeared at late stages, and secondly, that they were detected simultaneously along all axonemes within a cyst. Immunofluorescence on semithin sections and electron microscopic immunocytochemistry on ultrathin sections confirmed that the appearance of the epitope recognized by the monoclonal antibody occurred at the time of the individualization process of spermatids in D. melanogaster. These results indicate that the posttranslational modification occurs as a very late event, after complete assembly of axonemal microtubules, and that the axonemal tubulin becomes modified when axonemal microtubules become coupled with the membrane, suggesting that the modification may in some way be induced by the microtubule-membrane interaction.

Worried, worn out and angry: providing relief for caregivers.

Caregiving for elder family members is a growing national phenomenon. As such, new stressors for family members are being identified. This paper reports the perceptions of caregivers of elder adults about their caregiving role. Caregivers reported being worried, worn-out and angry. Furthermore, caregivers reported that their needs are not being met. The authors suggest strategies to provide relief for caregivers and for intervening with caregiving dyads.

Local fibrinolysis for superior mesenteric artery thromboembolism.

A 66-year-old man with atrial fibrillation was referred soon after developing left lower limb and abdominal pain with rectal bleeding. An immediate flush aortogram showed embolic occlusion of the left distal superficial femoral artery and superior mesenteric artery (SMA), 3 cm from its ostium. Recombinant tissue plasminogen activator (rtPA) 40 mg was selectively instilled in the SMA in two boluses. Abdominal symptoms resolved within 48 h, and complete recanalization of the SMA was shown on angiography. Exploratory laparotomy after 72 h showed a normal small bowel and right colon, and was completed by femoropopliteal embolectomy. Six months later, the patient remained asymptomatic.

[Profile of microbiological analyses needed for hospitalized clients at the Maisonneuve-Rosemont hospital]. / Profil des besoins en analyses microbiologiques de la clientèle hospitalisée à l'Hôpital Maisonneuve-Rosemont.

During five consecutive administrative periods, a computer data bank was set up from informations written on laboratory forms requesting tests in microbiology. A total of 13,260 forms were received and 11,591 were included in our study. 7,010 tests (60%) were requested from medical specialties; 40% of these tests were from patients admitted on hematology and on pediatrics wards. Of the 4,581 remaining tests, 36% were ordered for patients admitted on general surgery and on ophthalmology wards. Medical patients had three times as much blood cultures requested than surgical patients. The numbers of urine cultures done for medical and surgical patients were however similar (1,832 and 1,699 respectively). The average cost for microbiology cultures was twice as much in medical than in surgical patients. Such analysis of prescribing profile for laboratory tests provides useful information for the diagnosis related groups (DRG) system and can allow for a more efficient distribution of hospital resources.