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.

Relations between fatty acids and oestrogen binding properties of pure rat alpha 1-foetoprotein.

A delipidation procedure based on treatment with charcoal at pH 3 has been applied to highly purified rat alpha 1-foetoprotein preparations. The oestrogen binding properties of the delipidated proteins have been studied with an equilibrium dialysis technique, and compared with the properties of the untreated foetal protein, as well as those of preparations reconstituted from the defatted alpha 1-foetoprotein and the removed lipids. An important increase has been evidenced for the binding levels of oestrone, oestradiol-17 beta and diethylstilboestrol by the delipidated alpha 1-foetoprotein. A reversal of this effect has been obtained by incubating the delipidated protein either with the lipids extracted from the purified alpha 1-foetoprotein or with a potent competitor of the rat alpha 1-foetoprotein-oestrogen interaction, designated as 'L', previously demonstrated and isolated from whole rat sera, and tentatively characterized as a mixture of fatty acids. Scatchard analysis of the oestrone and oestradiol-17 beta binding parameters show that the enhanced fixation of the hormones after defatting is primarily due to a two-fold increase of the apparent number of binding sites/mol alpha 1-foetoprotein. The results are interpreted in terms of the probable, at least partial, identity between the lipids closely associated with the pure alpha 1-foetoprotein and the fatty acid mixture 'L' isolated from whole sera. The possible biological role of complex interplay between oestrophilic alpha 1-foetoproteins, phenolsteroids and fatty acids in the control of oestrogen levels during development is discussed briefly.

Age-dependent responses of the serum non-esterified fatty acids to adrenalectomy and ovariectomy in developing rats.

We report detailed gas chromatography analyses of the non-esterified fatty acids in the sera of female rats during post-natal maturation. A marked age-dependent decrease of concentration is demonstrated for all classes of compounds. Total levels fall from about 0.8 mM at birth to about 0.25 mM, 60 days later. The decrease is most pronounced for the polyunsaturated acids, which represent 27 +/- 9% of total fatty acids at birth and 13 +/- 3% 60 days later. The effects of ovariectomy and adrenalectomy on the free fatty acid levels as a function of age are strikingly different before and after maturation. When ovariectomy is performed at 5, 9 and 15 days, the fatty acid levels respond by a significant (30-40%) decrease; when adrenalectomy is carried out at the same ages, a dramatic 3-5-fold increase of all classes of fatty acids is observed. By contrast, in older animals, both responses have virtually disappeared. Possible mechanisms underlying the age-dependent patterns and behaviour of the serum free fatty acids are briefly discussed.

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.

Computer system for a hospital microbiology laboratory.

An online computer system has been developed for a university hospital laboratory in microbiology that processes more than 125,000 specimens yearly. The system performs activities such as the printing of reports, fiscal and administrative tasks, quality control of data and technics, epidemiologic assistance, germ identification, and teaching and research in the different subspecialties of microbiology. Features of interest are smooth sequential transmission of clinical microbiologic test results from the laboratory to medical records, instantaneous display of all results for as long as 16 months, and updating of patient status, room number, and attending physician before the printing of reports. All data stored in the computer-file can be retrieved by any data item or combination of such. The reports are normally produced in the laboratory area by a teleprinter or by batch at night in case of mechanical failure of the terminal. If the system breaks down, the manually completed request forms can be sent to medical records. Programs were written in COBOL and ASSEMBLY languages.

The role of nonesterified fatty acids and of alpha 1-fetoprotein in estrogen-dependent endocrine systems.

We discuss the various experimental findings to date that indicate that AFP may be considered as a positive or negative modulator of estrogenic action. Moreover, we show that this protein, even when nonestrogenophilic, is able to bind other hydrophobic ligands, in particular nonesterified fatty acids. These fatty acids inhibit the binding of estrogens to murine AFP as well as to the cytosolic estrogen receptors. Thus, the AFPs of all species--whether or not estrogenophilic--might play an endocrinologic role through the intermediary of the unsaturated fatty acids to which they associate with high affinity.

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.

Rat and human embryo and post-natal sera contain a potent endogenous competitor of estrogen-rat alpha-fetoprotein interactions.

A highly active inhibitor of the binding of estrone and estradiol-17beta to rat alpha-fetoprotein is demonstrated for the first time in embryo, immature and adult rat sera as well as in fetal and adult human sera. The competitive character and the narrow specificity of this inhibition effect is shown. The major compound responsible for this activity is isolated by successive column Sephadex LH20 and thin layer chromatography: it is characterized as a nonpolar, nonphenolic, dialysable and thermostable substance, unreactive towards anti-estrone and anti-estradiol-17beta antibodies. The possible biological role of an endogenous non-estrogen ligand of rodent fetoproteins is discussed.

[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.

[A thousand obstetrical sutures of the perineum using a slow absorption synthetic suture material (author's transl)]. / Un millier de sutures périnéales obstétricales avec un matériel de suture synthétique à résorption lente.

A thread which is absorbed slowly and which has a polyglycolic acid base has been used since 1975 in the Sainte-Foy-les-Lyon Maternity Unit to sew up episiotomies and perineal tears. The authors had 98.70 p. 100 of excellent results out of 1082 cases from the anatomic, aesthetic and functional angle. This technique appears to be a useful one in early mobilisation in obstetrics.

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.

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.

[Ruptured adenoma of the liver with severe pulmonary embolism discovered during a cesarean section]. / Adénome rompu du foie avec embolie pulmonaire grave découvert lors d'une césarienne.

A ruptured adenoma of liver was detected during a caesarean in a multipara woman at full term with a severe pulmonary embolus. Therapy for this rare and curious case, with combined internal hemorrhage, severe pulmonary embolism and full term pregnancy in a multipara, is discussed.