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International audience; Background: There is a growing need for real-world data on cancer treatments usage, especially to assess compliance with recommendations. We developed a French project using hospital data to analyse evolution in the therapeutic strategies implemented in patients with human epidermal growth factor receptor 2 (HER2)-overexpressed (HER2+) breast cancer (BC) and exposed to injectable HER2-targeted therapies, i.e. trastuzumab, pertuzumab or trastuzumab emtansine (T-DM1).Patients and methods: Data from 26,350 women with BC were extracted in September 2018 from the Electronic Pharmacy Record systems of 120 French randomly recruited hospitals. Evolution in the treatments used, and combination regimens were described from 2011, in accordance with the BC stage and treatment line.Results: Overall, 21,119 patients treated since 2011 were analysed: 16,398 patients with early BC (eBC) and 6030 patients with metastatic BC (mBC) including patients treated at both stages. In eBC, 89.2% of patients received trastuzumab combined with at least taxanes (trastuzumab-taxane-anthracycline: 62.6%). Patients with mBC were treated in the first line (80.3%) and/or the second line (40.1%) and/or ≥ the third line (28.3%). After its approval in 2014, pertuzumab was first used in first-line therapy combinations in 67.4% of the total cases, while trastuzumab-taxane decreased from 47.2% to 9.2%. Similarly, T-DM1 was used as the second-line treatment in 53.8% of cases.Conclusions: Given recent changes in available treatments for patients with HER2+ BC, this large French project provides robust information on real-world evolution in therapeutic strategies. Our data suggest there is room for significant improvement in optimal drug utilisation. Such data will be useful to build drug-related indicators for future value-based pricing solutions.

Let S S be a complete, open simply connected surface. Suppose that the integral of the Gauss curvature over arbitrary measurable sets is less than π / 2 \pi /2 in magnitude. We show that the surface admits a global Tchebychev net.

International audience; BACKGROUND & AIMS: We aimed at determining the effect of maintenance therapy with ribavirin alone, after a year of combined peginterferon-alfa 2a (PegIFNα-2a) and ribavirin therapy, on viral response and liver histology after liver transplantation (LT). METHODS: Hundred and one patients with recurrent HCV and a minimum of stage 1 fibrosis (METAVIR scoring), 1-5years after LT, were enrolled. PegIFNα-2a and ribavirin were initiated at 90 μg/wk and 600 mg/d, respectively, then increased or adjusted as a function of tolerance. At 12 months, combination therapy was discontinued and patients were randomized to ribavirin or placebo for a further 12 months. Growth factor use was permitted. RESULTS: At 18 months, a sustained virological response (SVR) was obtained in 47.9% of patients in Per Protocol (PP) analysis, and was higher in patients with genotype 2 or 3 than in patients with genotype 1 or 4, in patients with genotypes 1+4 receiving ciclosporine than in those receiving tacrolimus, in patients with worse renal function, in those having received EPO, in patients with lower weight, and in those with lower viral load at 3 months. Using logistic regression, only the early viral response, recipient weight and renal function were independently associated with better SVR. SVR, viral load, activity, and fibrosis scores were similar, at M18 and M30, in patients randomized to ribavirin, or to placebo. CONCLUSIONS: A PP SVR was achieved in 47.9% of patients with established recurrent hepatitis C after LT. Maintenance therapy with ribavirin alone does not improve the virological response or the histological parameters.

The aim of this observational study in patients with chronic hepatitis C and treated with interferon alpha-2a was to assess 1) monitoring in everyday practice, 2) the acceptability of treatment and 3) the intensity of fatigue.Three hundred and fifty four patients were enrolled by physicians in both teaching and general hospitals, or private practice. Before treatment, clinical, epidemiological, and virological data were collected as well as a self-evaluation of fatigue using a visual analogic scale. Clinical follow-up was assessed every 3 months during treatment and 6 months after the end of treatment and included an evaluation of fatigue and the number of workdays missed due to sickness.Two hundred and nineteen men and 135 women, mean age 45 +/- 13, were included. The epidemiological, histological and virological features of this group were similar to those patients usually treated for chronic hepatitis C. Before treatment, the mean measurement of fatigue was 41 on a scale from 0 (perfect form) to 100 (exhausted). Fatigue was unrelated to age, source of infection, biological activity, or histological score. It worsened in patients who stopped interferon after 3 or 6 months, but was stable in patients who continued treatment for 12 months. Fatigue decreased after the end of treatment and was unrelated to treatment response. The need to stop work was strongly related to the intensity of fatigue and the number of workdays missed due to sickness represented nearly two months out of three in 25% of active patients during the first quarter and in 15% of patients thereafter. 61% of patients self-injected interferon (mainly previous drug users) whereas 30% of patients used nurse care throughout treatment.This study not only provides a realistic evaluation of fatigue in patients with chronic hepatitis C, before, during and after treatment, but also highlights its social and economic consequences. It shows the need for further cost-effectiveness studies on new therapeutic strategies using combined treatments.

Percutaneous catheter drainage is a standard therapy for management of selected intra-abdominal abscesses. We describe three patients in whom this technique caused complicated thoracic empyemas. All patients required thoracotomy for decortication despite initial thoracostomy tube drainage. In each case, the percutaneously placed drainage catheter was found traversing the costophrenic angle, leading to direct communication between the pleural space and the abscess cavity. Review of the anatomic relationships of the inferior pleural margin to the lower ribs may help prevent this technical error.

We report recent experience with a new device, the thoracic vent, in the management of simple pneumothorax. There were 16 patients aged 19 to 73 years who suffered pneumothorax due to spontaneous (4), traumatic (3), or iatrogenic (9) causes. Ease of insertion, patient tolerance, and the presence of a unique signal diaphragm all contributed to patient and physician acceptance of the device. Average time to pneumothorax resolution was 2.5 days, and time to thoracic vent removal averaged 3.2 days. There were no immediate recurrences or significant complications. We conclude that the thoracic vent is an effective device for initial and definitive therapy of simple pneumothorax. (Chest 1991; 100:880-82)

Although more than 1 percent of black women 80 years of age or older have hip fractures each year, little is known about risk factors for hip fracture in these women.We carried out a case-control study involving 144 black women admitted with a first hip fracture to 1 of 30 hospitals in New York and Philadelphia. The control were 218 black women living in the community who were matched to the case patients according to age and ZIP Code or telephone exchange and 181 hospitalized black women matched according to age and hospital. Information was obtained through personal interviews and was studied by multivariable logistic-regression analysis.When the case patients were compared with the control subjects from the community, the women in the lowest quintile for body-mass index had a markedly increased risk of hip fracture as compared with the women in the highest quintile (odds ratio, 13.5; 95 percent confidence interval, 4.2 to 43.3). Postmenopausal estrogen therapy for one year or more was protective for women under 75 years of age (odds ratio, 0.1; 95 percent confidence interval,0.1 to 0.5). Factors associated with an increased risk of hip fracture included a history of stroke (odds ratio, 3.1; 95 percent confidence interval, 1.2 to 8.1), use of aids in walking (odds ratio, 5.6; 95 percent confidence interval, 2.7 to 11.5), and consumption of seven or more alcoholic drinks per week (odds ratio, 4.6; 95 percent confidence interval, 1.5 to 14.1). The results were similar when the case patients were compared with the hospitalized control subjects.Among black women thinness, previous stroke, use of aids in walking, and alcohol consumption are associated with an increased risk of hip fracture. Postmenopausal estrogen therapy protects against hip fracture in women under 75 years of age.

A technique called voiding urohydropropulsion has been developed that facilitates nonsurgical removal of urocystoliths. Voiding urohydropropulsion was performed in 11 dogs and 10 cats with urocystoliths. Urocystoliths were completely removed from 15 of 21 animals (5 female dogs, 3 male dogs, 5 female cats, and 1 male cat). The number of uroliths removed from any animal varied between 1 and 983. The mean time required to complete voiding urohydropropulsion in the 15 animals from which all uroliths were completely removed was 22 minutes. In 6 animals (2 female dogs, 3 female cats, and 1 male cat), not all urocystoliths were removed. Visible hematuria was induced in all animals as a consequence of voiding urohydropropulsion. In dogs, visible hematuria resolved within 4 hours. Dysuria was not induced by this technique in dogs. In many cats, visible hematuria and dysuria persisted for 1 to 2 days. One male cat developed urethral obstruction after we failed to remove a urolith from the bladder. The urolith was returned to the urinary bladder, and subsequently removed by cystotomy. Voiding urohydropropulsion is a simple and effective method that should be considered for removal of small urocystoliths from dogs and cats before cystotomy is performed.

We report recent experience with a new device, the thoracic vent, in the management of simple pneumothorax. There were 16 patients aged 19 to 73 years who suffered pneumothorax due to spontaneous (4), traumatic (3), or iatrogenic (9) causes. Ease of insertion, patient tolerance, and the presence of a unique signal diaphragm all contributed to patient and physician acceptance of the device. Average time to pneumothorax resolution was 2.5 days, and time to thoracic vent removal averaged 3.2 days. There were no immediate recurrences or significant complications. We conclude that the thoracic vent is an effective device for initial and definitive therapy of simple pneumothorax.

Engagement of the T-cell antigen receptor (TCR) induces the assembly of signaling complexes comprised of adapter molecules and enzymes. We use multiple approaches in our characterization of these complexes and the process of signal transduction mediated by the TCR. Our genetic approach is the study of mutations in a critical adapter molecule, LAT. Some of these mutations lead to an interesting lympho-proliferative disorder. Signaling complexes can be studied in vitro using biochemical and biophysical methods to determine the rules of signal complex formation. Finally, we visualize the formation and fate of multi-protein complexes at the site of TCR activation. To do so, we express various fluorescently-tagged signaling proteins in T cells and observe clusters of molecules containing the TCR and important adapters and enzymes. Direct imaging of signaling molecules has revealed the highly dynamic nature of molecular interactions at the TCR.

Two investigations used the instrumental-expressive role distinction to shape counseling behaviors and found these orientations differentially affecting subjects' preferences for therapists. Though similarity of role failed to influence choice of therapists, subjects who devalued their ability to cope with a psychological problem were attracted to the instrumental therapist, gave the therapist more responsibility for treatment outcome, and showed stronger identification with an opposite-sex parent.

Surgical treatment of gastroesophageal reflux has been thought to depend on the construction of a valve mechanism at the gastroesophageal junction (GEJ). Recently, a silicone prosthesis that does not construct a valve has been introduced, and in preliminary studies in the human, shown to be effective in the treatment of reflux. A precise mode of action has not been demonstrated for the prosthesis. This study was undertaken to investigate the mechanics of the prosthesis and determine its effectiveness in an animal model. Six canine gastroesophageal specimens were excised and the lower esophageal sphincter (LES) simulated by a rubber band placed around the GEJ at a tension calibrated to give 25 mmHg "sphincter" pressure. Circumferential silk ligatures of varying length were then placed on the stomach 3.0 cm distal to the GEJ. With no ligature, the LES opening pressure (LESOP) was 8.0 mmHg, varying to 17.0 mmHg with an 8.0 cm ligature. Further, 24 adult mongrel dogs were randomly divided into four equal groups: controls, circular myomectomy of the LES alone, myomectomy combined with fundoplication, and myomectomy combined with implantation of the silicone antireflux prosthesis. Evaluation included manometry, endoscopy, and histology. Although only the normal sphincter and fundoplication responded physiologically, the prosthesis was just as effective in preventing reflux, as evidenced by reducing acid exposure time of myomectomized dogs from 35.4% to 1.8%, and by preventing endoscopic esophagitis. It was concluded that the silicone antireflux prosthesis acts in the same fashion as the ligature in the model, by interrupting distraction of the LES by gastric wall tension. This concept is an effective method for raising LESOP, treating experimental gastroesophageal reflux, and eliminating the sequelae of reflux. Long-term evaluations of the prosthesis are required.

During a 15-year period, 62 patients were treated for achalasia of the esophagus. Pneumatic dilation (PD) had been performed initially in 46 and was successful in 23; failures were due to acute perforation of the esophagus, persistent dysphagia, or pathologic gastroesophageal reflux. Esophagomyotomy alone (EM) was performed in 19 individuals resulting in definite improvement in 12; four patients had moderate reflux or dysphagia, and three of these required another surgical procedure. An extended myotomy with an antireflux procedure (M-NF) was performed in 13 patients with symptomatic relief in 12; one patient required reconstruction of a too-tight fundoplication that caused persistent dysphagia. The advantages of pneumatic dilation were the ease of performance, patient acceptability, and an overall efficacy of 50%. Definitive surgical therapy, while more predictably effective in relieving dysphagia, was considerably more expensive in terms of patient discomfort and time. When pathologic reflux was present following a previous procedure, the M-NF was performed; obstruction of the esophagus did not occur if the fundoplication was "floppy." The M-NF deserves consideration as the surgical procedure of choice for achalasia.

The isolation and characterization of oncogenes from human colon cancer and the recognition of their homology with the ras gene of the Harvey and Kirsten strain of murine sarcoma virus (MSV) led us to investigate the effect of exogenous MSV on 1,2 dimethylhydrazine (DMH)-induced colon carcinoma in rats. DMH, 20 mg base/kg, was injected weekly for 10 weeks into Sprague-Dawley rats. The Moloney murine sarcoma virus (MSV-M) was injected (200 focus-forming units) intraperitoneally into 15 rats 48 hours after the last DMH injection or in 12 rats before the first DMH injection. Controls consisted of 12 rats receiving 10 injections of DMH only, nine rats receiving MSV-M alone, and 10 untreated rats. All tumors induced were adenocarcinomas of the gastrointestinal tract, characteristically induced by DMH and not by MSV-M. In the late virus group there was an augmentation of colon tumor induction (mean, 2.2 versus 1.1 colon tumors/rat, p less than 0.05), and in the MSV pretreated group, there was also significant augmentation of colon tumor induction (mean, 2.4 versus 1.1 colon tumors/rat, p less than 0.005) when compared with rats treated with DMH alone. Rats treated with MSV-M alone and untreated rats had no tumors. This is the first study to suggest the importance of exogenous viral infection in chemically induced colonic carcinogenesis.

A new technique for inserting and securing large bore intravenous lines directly into the right atrium, to be used in patients requiring a thoracotomy in the emergency room, is described herein. A plastic clip is attached to the edge of the atrial appendage and holds a large catheter in place. We have used this new technique successfully at the Cook County Hospital Trauma Unit and have encountered no complications to date.

Oleic acid has been found in cooked beef and human feces. It has also been found to protect against mutagenesis as measured by the Salmonella microsomal assay test. Addition of oleic acid to the diet of rats treated with, 1,2-dimethylhydrazine, a colon carcinogen, failed to protect the rats against the induction of colon cancer.

• Of 522 children with acute appendicitis treated from 1978 to 1985, 170 had appendiceal perforation with peritonitis. The protocol for perforation included aggressive fluid resuscitation, preoperative triple antibiotic therapy, copious peritoneal lavage, avoidance of transperitoneal drains except those used for well-localized abscesses, delayed wound closure, and postoperative antibiotic therapy for seven to ten days. The minor complication rate was 22%; this included pleural effusion, wound infection, atelectasis, and prolonged ileus. The major complication rate was 3%; this included intra-abdominal abscess, gastrointestinal bleeding, wound dehiscence, pneumonia, and intestinal obstruction. Only four postoperative intra-abdominal abscesses occurred, in three patients. The mortality rate was zero. A comparison of this series with a similar group of 24 patients who underwent drainage showed the relative rate of abdominal abscess formation to be 1.8% (undrained) vs 12.5% (drained). We achieved our lowest rate of serious complications following surgery for pediatric perforated appendix with the use of aggressive fluid resuscitation, broad-spectrum antibiotic therapy, copious peritoneal irrigation, and delayed wound closure and without drainage. (Arch Surg1987;122:691-696)

There is epidemiological evidence that populations with alkaline stool pH are at greater risk for colon cancer than populations with acid stool pH. This association was investigated in the laboratory using the rat-dimethylhydrazine colon carcinogenesis model. Rats with acid stool pH, produced by consumption of lactulose or sodium sulphate or both, had significantly fewer colon tumours after injections of dimethylhydrazine (DMH) than rats treated with DMH alone. The results confirm the hypothesis that acidification of the stool can protect against the induction of colon cancer.

There is an epidemiologic association between beer consumption and rectal cancer. Beer and ethanol were tested in the rat-dimethylhydrazine (DMH) experimental carcinogenesis model in order to verify this observation. Ethanol was found not to affect the number of colonic tumors induced by DMH (86 vs. 77 controls, P = 0.764). In rats fed beer and treated with DMH, there was a decrease in gastrointestinal tumor induction (P = 0.043). This instance then becomes one of many in which conclusions drawn from epidemiologic studies have been contradicted when subjected to analysis in an experimental colon carcinogenesis model.