Compliance with the pregnancy prevention program among women initiating isotretinoin treatment between 2014 and 2021: A nationwide cohort study on the French Health Data System (SNDS).

BACKGROUND: Despite the French pregnancy prevention program (PPP), a considerable number of pregnancies are potentially exposed to oral isotretinoin. New measures were taken by the French Medicines Agency, including the restriction of initial isotretinoin prescriptions to dermatology specialists in May 2015 and a new information campaign on teratogenicity in January 2019. OBJECTIVES: The aims were to: describe, between 2014 and 2021, compliance with PPP recommendations: isotretinoin use as a second-line treatment, first prescription by a dermatology specialist, monthly prescription renewal and pregnancy testing (PT); assess the effect of the 2015 and 2019 measures on PT compliance; and identify the determinants of PT noncompliance. METHODS: A retrospective cohort study was conducted among women aged 11-50 years initiating isotretinoin between 2014 and 2021 using the French Health Data System. PT compliance corresponded to pregnancy test completion and specific delays between prescription and dispensation. Time series analyses were performed to evaluate the effect of the 2015 and 2019 measures on PT compliance, and log-binomial and Poisson multivariate regression models were used to identify the determinants of PT noncompliance. RESULTS: Isotretinoin was prescribed as a second-line treatment in 64% of initiations, mainly by dermatology specialists (92%). A new monthly prescription was observed in 98% of dispensations. PT compliance reached 61%, 72% and 25% at initiation, renewals and end of treatment, respectively. The 2015 measure was associated with better PT compliance at initiation and renewals. The 2019 measure had no significant effect on PT compliance at the initiation or end of treatment but was associated with a decrease in PT compliance at renewals. Age, low socioeconomic level, initiation by a nondermatology specialist and during summer were associated with PT noncompliance. CONCLUSIONS: Understanding factors associated with PT noncompliance could help to target specific subpopulations of women treated with isotretinoin.

How does gatekeeper training improve suicide prevention for elderly people in nursing homes? A controlled study in 24 centres.

BACKGROUND: The death rate due to suicide in elderly people is particularly high. As part of suicide selective prevention measures for at-risk populations, the WHO recommends training "gatekeepers". METHODS: In order to assess the impact of gatekeeper training for members of staff, we carried out a controlled quasi-experimental study over the course of one year, comparing 12 nursing homes where at least 30% of the staff had undergone gatekeeper training with 12 nursing homes without trained staff. We collected data about the residents considered to be suicidal, their management further to being identified, as well as measures taken at nursing home level to prevent suicide. RESULTS: The two nursing home groups did not present significantly different characteristics. In the nursing homes with trained staff, the staff were deemed to be better prepared to approach suicidal individuals. The detection of suicidal residents relied more on the whole staff and less on the psychologist alone when compared to nursing homes without trained staff. A significantly larger number of measures were taken to manage suicidal residents in the trained nursing homes. Suicidal residents were more frequently referred to the psychologist. Trained nursing homes put in place significantly more suicide prevention measures at an institutional level. CONCLUSIONS: Having trained gatekeepers has an impact not only for the trained individuals but also for the whole institution where they work, both in terms of managing suicidal residents and routine suicide prevention measures.

Preoperative CT and MRI prediction of non-resectability in patients treated for pseudomyxoma peritonei from mucinous appendiceal neoplasms.

AIMS: To evaluate computed tomography (CT) and magnetic resonance imaging (MRI) findings for sign of hepatoduodenal ligament and small bowel non-resectability in patients with pseudomyxoma peritonei (PMP) and to compare assessments made by the radiologist based on their experiences. METHODS: Between January 2009 and June 2014, all consecutive patients with PMP selected for curative surgery were scheduled to undergo CT and MRI examinations within two days of their surgery. Several imaging findings of hepatoduodenal ligament and small bowel involvements were retrospectively evaluated by a senior and a junior radiologist and compared with surgical findings. RESULTS: Of the 82 patients enrolled in the study, 11 had non-resectable lesions with hepatoduodenal ligament infiltration (n = 4) and/or extensive small bowel involvement (n = 9). All patients underwent CT and 73 underwent MRI scan. Infiltration of the adipose tissue of the hepatoduodenal ligament by mucinous tumor was associated with non-resectability. For the senior and junior radiologists, the sensitivity and specificity were 75% and 100%, and 50% and 100% on CT (kappa value (k) = 0.79); 67% and 100%, and 33% and 97% on MRI (k = 0.38), respectively. Diffuse involvement of the mesentery and/or the small bowel serosa was also associated with non-resectability. For the senior and junior radiologists, the sensitivity and specificity were 67% and 100%, and 56% and 99% on CT (k = 0.82); 88% and 100%, and 38% and 100% on MRI (k = 0.58), respectively. CONCLUSION: CT and MRI can both contribute to the diagnosis of non-resectability in patients with PMP. The use of MRI to identify small bowel involvement, in particular, benefits from a more experienced radiologist.

Influence of observable and unobservable exposure on the patient's risk of acquiring influenza-like illness at hospital.

During outbreaks of hospital-acquired influenza-like illness (HA-ILI) healthcare workers (HCWs), patients, and visitors are each a source of infection for the other. Quantifying the effects of these various exposures will help improve prevention and control of HA-ILI outbreaks. We estimated the attributability of HA-ILI to: (1) exposure to recorded or unrecorded sources; (2) exposure to contagious patient or contagious HCW; (3) exposure during observable or unobservable contagious period of the recorded sources; and, (4) the moment of exposure. Among recorded sources, 59% [95% credible interval (CrI) 34-83] of HA-ILI of patients was associated with exposure to contagious patients and 41% (95% CrI 17-66) with exposure to contagious HCWs. Exposure during the unobservable contagiousness period of source patients accounted for 49% (95% CrI 19-75) of HA-ILI, while exposure during the unobservable contagiousness period of source HCWs accounted for 82% (95% CrI 51-99) of HA-ILI. About 80% of HA-ILIs were associated with exposure 1 day earlier. Secondary cases of HA-ILI might appear as soon as the day after the detection of a primary case highlighting the explosive nature of HA-ILI spread. Unobservable transmission was the main cause of HA-ILI transmission suggesting that symptom-based control measures alone might not prevent hospital outbreaks. The results support the rapid implementation of interventions to control influenza transmission.

[Description of patients with confirmed influenza A(H1N1)pdm09 admitted to an intensive care unit and identification of severity risk factors]. / Description des cas confirmés de grippe A(H1N1)pdm09 admis en réanimation et identification des facteurs de gravité

OBJECTIVE: The authors had for objective to describe patients with confirmed influenza A(H1N1)pdm09 admitted to an intensive care unit (ICU) in a university hospital and to identify risk factors correlated with the severity of the disease. DESIGN: A prospective study was conducted in an university hospital during the A(H1N1)pdm09 influenza pandemic. Severe laboratory confirmed cases (admitted to an ICU) were described and compared with non-severe confirmed cases (not admitted to an ICU). RESULTS: Sixty-nine patients were included; 36 (52%) were 15 to 44 years of age. Sixteen (23%) cases were defined as severe, ten of these (63%) concerned patients 45 to 64 years of age. The independent factors associated with severity were: a history of heart disease, obesity, and tobacco abuse. CONCLUSIONS: This work reinforces the need to identify and protect groups at risk of severe outcomes.

[Treatment of childhood dystonia]. / Traitement des dystonies de l'enfant.

Dystonia is not uncommon in childhood, but is clinically very heterogeneous. Therefore, introduction and follow-up of the treatment of dystonia in children are often a challenge for the physicians. Progresses in functional neurosurgery have open new fields in the treatment of dystonia in children, but it should be managed by a multidisciplinary team. This paper reviews the various therapeutic options available for childhood-onset dystonia, with a specific attention to dosage and side effects of the drugs regarding pediatric population according to the data of the literature. The rational strategy for therapeutic management of the various types of childhood dystonia is discussed.

Fossil fuel biomarkers in sewage sludges: environmental significance

Fossil fuel biomarkers, or "molecular fossils," are specific organic substances found in coals, petroleums, and sedimentary rocks. They are formed during millions of years of sedimentary burial by geochemical alteration of biological molecules, such as cholesterol, under the effect of biodegradation, temperature, pressure, and mineral catalysis, to produce geochemically mature molecules, for example, aromatic steroids (Fig. 1). Since fossil fuel biomarkers have a very specific molecular structure betraying fossil fuel sources, such markers should be useful in assessing the fossil fuel contamination of various modern media such as soils, plants, waters, and modern sediments. Here the identification of fossil fuel biomarkers of high geothermal maturity in sewage sludges provides evidence of the contamination of sludges by petroleum products. The most likely sources of contamination are contaminated vegetal food, road dust, and soil particles carried by rain water.http://link. springer.de/link/service/journals/00114/bibs/9086010/90860484. htm

Characterization of extractable species from poly(etherurethane urea) (PEUU) elastomers.

Methanol extracts of four poly(etherurethane urea) (PEUU) materials were analyzed using Gel Permeation Chromatography (GPC). The additives in the materials were Santowhite powder at 1 wt% and Methacrol 2138 F at 5 wt% loading levels. One-to-two wt% of the original PEUU films was extractable with methanol. The extractables consisted of a low molecular weight (Mw) PEUU polymer, an MDI-rich oligomer, the additives Santowhite (SW) powder and Methacrol 2138 F, and aniline. The low Mw PEUU polymer had a Mw of 12,000 relative to polystyrene, and the MDI-rich oligomer had a Mw of 1000 relative to polystyrene. Quantitation of all extracted species was achieved using GPC; the use of dual-detectors on the GPC made it possible to determine the soft-to-hard composition of the PEUU extracts as a function of molecular weight.

Attachment and proliferation of bovine aortic endothelial cells onto additive modified poly(ether urethane ureas).

To better understand endothelial cell interactions with poly(ether urethane urea) (PEUU) materials, and to assess bovine aortic endothelial cell attachment, films were incubated for 24 h with BAEC in media containing 5% fetal bovine serum. Other films were allowed to incubate for 4 more days in media containing 5% fetal bovine serum without cells to assess BAEC proliferation. The assay was performed on PEUU films modified with acrylate and methacrylate polymer and copolymer additives that spanned a wide range on the hydrophobicity/hydrophilicity scale. Tissue culture polystyrene (TCPS) was used as a control. The assay showed that PEUU films loaded with Methacrol 2138F [copoly(diisopropylaminoethyl methacrylate [DI-PAM]/decyl methacrylate [DM]) (3/1)] or with its hydrophilic component, DIPAM, in homopolymer form (i.e., h-DIPAM), significantly enhanced BAEC attachment (approximately 80% of TCPS values) and proliferation (approximately 80%) when compared to unloaded PEUU films (attachment 73%; proliferation, 47%) or to PEUU films loaded with the more hydrophobic acrylate or methacrylate polymer additives (attachment, 32-69%; proliferation, 18-57%). The assay also showed that PEUU films coated with homopoly(diisopropylaminoethyl acrylate) (h-DIPAA) significantly enhanced BAEC attachment and proliferation when compared to PEUU films coated with h-decyl acrylate (h-DA); films coated with the copolymer of these two acrylates (i.e., co-[DIPAA/DA] [3/1]) showed intermediate behavior. To explain the enhancement of BAEC interaction with films loaded with Methacrol 2138F or h-DIPAM, when compared to unmodified PEUU films or to PEUU films loaded with more hydrophobic acrylate and methacrylate polymer additives, it was assumed that the additives near the surface region of the solvent swollen PEUU matrix may have migrated to, or near to, the PEUU-air interface during film formation, creating an additive enriched PEUU surface region. It is suggested that, once at this surface region, dynamic reorientation in response to an aqueous medium ensured the additives were able significantly to influence protein adsorption, and concomitant endothelial cell behavior, but only if they interacted with aqueous media more favorably than the PEUU. The ability of Methacrol and h-DIPAM additives to enhance endothelial cell behavior is argued to be the result of increased hydrophilicity. This is the result of exposed, hydrogen-bonding DIPAM moieties and increased surface flexibility, which is itself due to the hydration of unhindered Methacrol chains, which may create an additive enriched PEUU-water interfacial zone.

Protein adsorption to poly(ether urethane ureas) modified with acrylate and methacrylate polymer and copolymer additives.

To understand better blood interactions with poly(ether urethane urea) (PEUU) materials, a radioimmunoassay and whole or diluted human plasma were used to characterize the presence of fibrinogen, immunoglobulin G, factor VIII/von Willebrand factor, Hageman factor (factor XII), and albumin on a PEUU formulation and on PEUU formulations modified with the amphiphilic additive Methacrol 2138F (co[diisopropylaminoethyl methacrylate (DIPAM)/decyl methacrylate] [3/1]), or with hydrophobic acrylate or methacrylate polymer or copolymer additives. The protein adsorption assay showed that PEUU films loaded or coated with Methacrol 2138F (Methacrol) or homopoly-DIPAM (h-DIPAM) adsorbed significantly lower amounts of the studied proteins than did either the base PEUU formulations or the PEUUs loaded with the more hydrophobic acrylate or methacrylate polymer additives. Experiments with Methacrol-loaded PEUUs, where the loading of Methacrol was varied from 0.25 wt% to 20.0 wt%, showed that the adsorption of each of the characterized proteins did not vary significantly throughout the Methacrol loading range, and that all Methacrol-loaded PEUU formulations adsorbed significantly lower amounts of the studied proteins than did the unloaded PEUU. Phase separation within the additive loaded PEUUs was characterized by scanning electron microscopy (SEM). The solubility parameters of the additives, as well as of the base PEUU, were calculated and used to interpret differences in phase separation of the additive modified PEUUs. The analysis showed that additives of lower solubility parameter phase-separated into fewer large microdroplets within the PEUU matrix. SEM analysis also showed that additive microdroplets were not present on the air side surface of loaded PEUUs. To explain the differences in protein adsorption to the air side of additive loaded PEUUs when compared to the base PEUU, it was assumed that the additives near this region of the solvent swollen PEUU matrix may have migrated to, at, or near the PEUU-air interface during film formation, creating an additive enriched PEUU surface region. Once at this surface region, it was suggested that dynamic surface reorientation in response to an aqueous medium ensured that the additives were able significantly to influence protein adsorption behavior only if they interacted with aqueous media more favorably than the PEUU.

Protein adsorption onto poly(ether urethane ureas) containing Methacrol 2138F: a surface-active amphiphilic additive.

Surface characterization and protein adsorption studies were carried out on a series of additive dispersed and additive coated poly(ether urethane ureas), PEUUs, to characterize early events in the blood compatibility of these materials. A hypothesis that is based on surface hydrophilicity, surface flexibility, and adsorption media has been developed to understand the modulated adsorption of plasma proteins by PEUU additives. Electron spectroscopy for chemical analysis (ESCA) and contact angle analysis were performed on two PEUU formulation as well as on PEUU formulations modified with Methacrol 2138F (co[diisopropylaminoethyl methacrylate (DIPAM)/decyl methacrylate (DM)][3/1]) or acrylate or methacrylate polymer or copolymer analogs of Methacrol 2138F. Methacrol 2138F is a commercially used amphiphilic copolymethacrylate. ESCA showed that the PEUUs loaded with Methacrol 2138F or with its hydrophilic component, homopoly (DIPAM) (h-(DIPAM)), had a higher percentage of nitrogen at their surfaces than did the base PEUUs. Contact angle analysis also showed that the air side of PEUU formulations loaded with Methacrol 2138F were more hydrophobic than was the air side of base PEUUs when films were cast from dimethylacetamide. However, during contact angle testing, the air side of PEUU films loaded with Methacrol 2138F rapidly became more hydrophilic than did the air side of the base PEUU films. A radioimmunoassay and whole or diluted human plasma were also used to characterize the presence of the proteins fibrinogen, immunoglobulin G, factor VIII/von Willebrand factor, Hageman factor (factor XII), and albumin, on the surface of the same PEUUs as analyzed by ESCA and contact angle. The protein adsorption assay showed that PEUU films loaded or coated with Methacrol 2138F, with a copolyacrylate analog of Methacrol 2138F (co(diisopropylaminoethyl acrylate [DIPAA]/decyl acrylate [DA]) [3/1]), or with the hydrophilic polyacrylate or polymethacrylate component analogs of Methacrol 2138F (h-DIPAM or h-DIPAA) adsorbed significantly lower amounts of the proteins than did either the base PEUU formulations or the homopoly(decyl methacrylate) (h-DM) or homopoly(decyl acrylate) (h-DA) coated or loaded PEUUs.

Infrared spectral analysis of extractables from poly(etherurethane urea) (PEUU) elastomers.

Poly(etherurethane urea) (PEUU) elastomers when employed as biomedical devices may be susceptible to extraction upon implantation. Four PEUU elastomers containing a single PEUU formulation, but varying in terms of their additives, were subjected to an in vitro extraction procedure. The additives in the PEUUs were Methacrol 2138 F at 5 wt% and Santowhite powder at 1 wt% levels. Only 1-2 wt% of the PEUUs was extractable with methanol. Fourier transform infrared spectroscopy (FT-IR) furnished qualitative and quantitative information on the extractables. The extractables consisted of a PEUU component that on the average was richer in soft segment than the bulk PEUU, and the two additives, Methacrol 2138 F and Santowhite powder.

Theoretical analysis on cell size distribution and kinetics of foreign-body giant cell formation in vivo on polyurethane elastomers.

The nature of in vivo leukocyte adhesion and foreign-body giant cell (FBGC) formation on polyurethanes was studied through theoretical and statistical analyses in terms of cell size distribution, density changes, and kinetics of FBGC formation. The results showed that the size distribution of FBGCs followed a "most probable" distribution. During FBGC formation, the densities of FBGCs changed with time. At an early stage, the number of FBGCs increased with time to a maximum at the expense of macrophages. As more FBGCs were formed and less macrophages were present, the fusion of FBGCs among themselves became significant. This, in turn, caused a gradual decrease of FBGC density with time. The rate of FBGC formation was characterized by a rate constant that represented certain characteristics of cell fusion and FBGC formation and the density of initial FBGC-forming macrophages that were a small fraction of leukocytes adhering to the surface. The direct correlations of surface cracking and pitting and adherent FBGCs demonstrated the influence of phagocytic actions of FBGCs on the biostability of implanted polyurethanes. While the cracking was thought to be caused by oxidative degradation facilitated by oxygen ion/radical release of FBGCs, the pitting appeared to result from the Methacrol 2138F aggregates diffusing out of the polymer in an acidic microenvironment under FBGCs, which in turn could be enhanced by the surface degradation and cell phagocytosis. The added Santowhite powder in polyurethane had a significant influence on FBGC formation: It reduced FBGC density and rate of FBGC formation by reducing leukocyte adhesion and the number of macrophages participating in FBGC formation.

Effect of some additives on the biostability of a poly(etherurethane) elastomer.

Four materials based on a single poly-(etherurethane) (PEU) prepared from MDI and PTMEG but differing in additives were studied in the cage implant system. The two additives studied were Santowhite powder at the 1% level and Methacrol 2138F 5%. Methacrol 2138F appeared to be immiscible with the base PEU and was dispersed in discrete domains about 0.5-micron in size. The retrieved PEU specimens were also cleaned and examined in the optical and scanning electron microscopes, and the size and density of adherent foreign body giant cells (FBGCs) were measured at implantation times up to 10 weeks. Methacrol 2138F had no effect on the density, coverage or size distribution of adherent FBGCs, but leaching of Methacrol 2138F was considered to be responsible for extensive pitting of the PEU surface. On the other hand, Santowhite powder appeared to inhibit formation of FBGCs, and while surface cracking and flaking were observed as early as 3 weeks postimplantation on some PEUs, the Santowhite powder effectively inhibited surface cracking and flaking up to the longest implantation time studied.

Gastric lymphomas: chemotherapy as a primary treatment.

Twenty-one of 65 patients with gastric lymphoma have been treated with combination chemotherapy; 17 patients had chemotherapy as primary treatment, and 4 had it for residual disease after incomplete surgical resection. Three of these patients were in stage III and 18 were in stage IV of the disease, according to the TNM Staging Classification. CHOP-Bleo or CHOP combination was given to 17 patients, and the COPP-Bleo regimen to three; the last one was treated with COP. Sixteen of the 18 stage IV patients entered into complete remission after 6 to 10 courses of CHOP or COPP-Bleo; there was one partial response and one failure. Six complete responders had a surgical restaging performed and none of them had gross evidence of residual disease; all of them had partial gastrectomy and in five cases there was no microscopical evidence of disease; in one of the resected stomachs, a focus of residual disease was discovered involving the submucosa but without compromise of the serosa. Fourteen (77.7%) of these patients are alive with no evidence of disease 1-10 (X = 3.8 years); one patient died with recurrent disease at 30 months; another patient died of other causes after 3 years; one patient is alive with disease at 18+ months. All the remaining 16 stage IV patients who were not given chemotherapy have died, median survival time being 5 months.(ABSTRACT TRUNCATED AT 250 WORDS)

[Combined chemotherapy with the FEM protocol in advanced gastric cancer]. / Quimioterapia combinada con el esquema FEM en cáncer gástrico avanzado.

Thirty one patients with diagnosis of Gastric Cancer were admitted in this study. Median age was 71 years (range 24-82). Twenty two were male. No one had previous chemotherapy. Functional capacity was 0-1 in 26/31 (60.6%). More common symptoms were: loss of weight 21/31 (75.1%) and abdominal pain in 13/31 (40.3%). Ten patients were Borrmann III and nine Borrmann IV. Twenty one had surgery: 12 palliative gastrectomy and 9 exploratory laparatomy. Twenty three cases were adenocarcinoma and 8 undifferentiated carcinoma. FEM regimen was administered (5 Fluoruracil 600 mg/m2/day 1 and 8, Epidoxorubicin 30 mg/m2/day 1 and Mitomycin 10 mg/m2/day 1). Ten of 24 patients (41.7%) achieved partial remission with a median survival of 10.5 months. Three patients achieved subjective response with a median survival of 6 months. Median survival for the non response was 3 months (range 2-7 months). Survival difference between responders and no responders was statistically significant. Survival among the adjuvent group was 5.7 months (range 2-16 months). One out of three patients survived without evidence of disease at the end of this study. Twenty three patients died and 5 were lost to follow up. Alopecia was the most common secondary effect in 74%, nausea and vomiting in 60% and leukopenia below 3000 x mm3 in 54%. Cardiotoxicity was not documented in any case.