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1 The effects of fluvoxamine to a maximum of 300 mg daily were compared with those of imipramine to a maximum of 200 mg daily, in 151 patients with primary major depression. 2 Four weeks of treatment with fluvoxamine resulted in 67.2% improvement (+/- s.d. 21.6) on the Hamilton Rating Scale for Depression (26 items). Treatment with imipramine showed 62.1% improvement (+/- s.d. 29.5) on this scale. 3 Fluvoxamine had no untoward effects on the cardiovascular system, while imipramine produced systematic increases in the postural fall in blood pressure. Dry mouth, nausea, daytime somnolence and tremor were seen with fluvoxamine treatment, while imipramine was associated with dry mouth, daytime somnolence, dizziness and tremor. 4 We conclude that fluvoxamine seems to have the same general antidepressant efficacy as imipramine. It was not associated with any safety problems and was generally well tolerated. [ABSTRACT FROM AUTHOR]

1. Fifty-four depressive in-patients aged 18-45 yr, were treated at random, in double-blind conditions, with mianserin 60 mg daily or imipramine 150 mg daily in three divided doses for 4 weeks. Nitrazepam and diazepam were also allowed if necessary. 2. There was no significant difference in antidepressant efficacy between the two groups, as assessed by the rating scales of Hamilton, Beck and Overall, the Brief Psychiatric Rating Scale, and a global clinical rating. 3. The overall frequency of side-effects was significantly lower with mianserin than with imipramine. Autonomic symptoms increased in severity during treatment with imipramine, but not with mianserin. 4. the patients treated with imipramine had a fall in blood pressure which was not observed during mianserin treatment. [ABSTRACT FROM AUTHOR]

Background and Objective: Failure rates after first-line treatment of localized prostate cancer (PCa) treatment remain high; therefore, it is essential to improve the selection and identification of at-risk patients to reduce mortality. The aim of the ANDROCAN study was to evaluate the biochemical recurrence (BCR) in patients with localized PCa treated by total prostatectomy at 5 yr after surgery, according to their presurgery gonadal status., Methods: A prospective cohort study was conducted including 1318 patients undergoing total prostatectomy for localized PCa with a 5-yr postoperative follow-up. Clinical and hormonal data (assays of total testosterone [TT], bioavailable testosterone [BT], dihydrotestosterone, estrone, and estradiol were performed by gas chromatography/mass spectrometry) as well as metabolic syndrome parameters were collected at baseline before surgery. Pathological data (predominant Gleason grade 4 and stage) were collected and cross-referenced centrally. Factors associated with BCR were assessed by a multivariate analysis, and BCR-free survival was assessed by a Kaplan-Meier analysis., Key Findings and Limitations: Among the 1318 patients, 237 had BCR of PCa. Considering demographic characteristics, populations with and without BCR were similar. However, patients with BCR had cancers with a higher Gleason score (p = 0.0001) and higher prostate-specific antigen (PSA) values (p = 0.0005) at baseline. Gleason score, pT >3a, and PSA level at baseline were positively correlated with BCR (p < 0.0001, p < 0.0001, and p = 0.0048, respectively), while BT and TT levels were not associated with BCR. This study includes patients with varying clinical characteristics, such as cancer history and metabolic syndrome, introducing variability that makes it challenging to isolate the specific effects of gonadal status on BCR. Another limitation is the lack of evaluation of long-term BCR beyond 5 yr, potentially overlooking recurrences that occur between 5 and 15 yr after surgery. This could lead to an underestimation of the actual long-term recurrence rates., Conclusions and Clinical Implications: Overall, PSA levels, high Gleason score, and pT >3a are associated with a greater likelihood of disease recurrence following initial treatment and could serve as important prognostic indicators for predicting the risk of BCR. In this prospective study, biochemical hypogonadism was not associated with a higher occurrence of BCR within 5 yr of prostatectomy. The biological gonadal status of preoperative patients could potentially be useful for therapeutic decisions but does not provide an indication for the oncological follow-up., Patient Summary: Five-year follow up of patients after surgery showed that there is no association between hypogonadism (low levels of total testosterone and bioavailable testosterone) and cancer recurrence. However, cancer recurrence seems to be more associated with aggressiveness of cancer at the time of detection., (Copyright © 2024 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Urinary tract infection (UTI) prevention benefits of cranberry intake are clinically validated, especially for women and children. To ensure the benefits of cranberry dietary supplement products, the anti-adhesion activity (AAA) against uropathogenic bacteria is routinely used in in vitro bioassays to determine the activity in whole product formulations, isolated compounds, and ex vivo bioassays to assess urinary activity following intake. D-mannose is another dietary supplement taken for UTI prevention, based on the anti-adhesion mechanism., Objective: Compare the relative AAA of cranberry and D-mannose dietary supplements against the most important bacterial types contributing to the pathogenesis of UTI, and consider how certain components potentially induce in vivo activity., Methods: The current study used a crossover design to determine ex vivo AAA against both P- and Type 1-fimbriated uropathogenic Escherichia coli of either D-mannose or a cranberry fruit juice dry extract product containing 36 mg of soluble proanthocyanidins (PACs), using bioassays that measure urinary activity following consumption. AAA of extracted cranberry compound fractions and D-mannose were compared in vitro and potential induction mechanisms of urinary AAA explored., Results: The cranberry dietary supplement exhibited both P-type and Type 1 in vitro and ex vivo AAA, while D-mannose only prevented Type 1 adhesion. Cranberry also demonstrated more robust and consistent ex vivo urinary AAA than D-mannose over each 1-week study period at different urine collection time points. The means by which the compounds with in vitro activity in each supplement product could potentially induce the AAA in urines was discussed relative to the data., Conclusions: Results of the current study provide consumers and healthcare professionals with additional details on the compounds and mechanisms involved in the positive, broad-spectrum AAA of cranberry against both E. coli bacterial types most important in UTIs and uncovers limitations on AAA and effectiveness of D-mannose compared to cranberry.

A number of clinical trials support the use of standardized cranberry supplement products for prevention of urinary tract infections; however, products that are not well-characterized for sufficient levels of bioactive components may contribute to negative clinical outcomes. Cranberry supplements for consumer use are not regulated and can be formulated different ways using cranberry juice, pomace or various combinations. This can lead to consumer confusion regarding effectiveness of individual products. The current study compared two commercial supplement products, one made from cranberry juice extract and the other from a blend of whole cranberry. The influence of formulation and proanthocyanidin (PAC) solubility on in vitro and ex vivo P-fimbriated Escherichia coli bacterial anti-adhesion activity (AAA) was determined. Both supplement products as well as whole, frozen cranberries were chromatographically separated into crude polyphenolic, sugar and acid fractions. In vitro AAA testing of all fractions confirmed that only those containing soluble PACs elicited activity. The cranberry juice extract product had higher soluble PAC content than the whole cranberry blended product, which contained mainly insoluble PACs. The influence of soluble and insoluble PAC levels in each product on the urinary (ex vivo) AAA was determined following ingestion. The juice extract product was associated with significantly higher urinary AAA than that of the whole berry blended product when consumed once daily over the 1-week intervention period.

This study aims to investigate whether clinical and biological preoperative characteristics of patients who were to undergo radical prostatectomy were associated with impairment in patient-reported quality of life (QoL) and erectile dysfunction immediately before intervention. We evaluated patient-reported outcomes among 1019 patients (out of 1343) of the AndroCan study, willing to score the Aging Male Symptom (AMS) and the International Index of Erectile Function 5-item (IIEF-5) auto-questionnaires. Univariate linear regression and robust multiple regression were used to ascertain the relationship between demographic, clinical, and hormonal parameters and global AMS or IIEF-5 scores. As a result, most patients (85.1') of the Androcan cohort agreed to complete questionnaires. Significantly higher IIEF-5 global scores were found in non-Caucasian and obese patients, with larger waist circumference, metabolic syndrome, diabetes mellitus, cardiovascular disease, hypertension, high blood sugar, concomitant medications, and hypogonadism, while the AMS global score was significantly higher in patients with larger waist circumference, metabolic syndrome, high blood pressure, raised glycemia, and concomitant medication. The IIEF-5 global score was correlated to age, dehydroepiandrosterone (DHEA), fat mass percentage, and androstenediol (D5). The AMS global score was significantly correlated to DHEA, D5, and DHEA sulfate. Finally, the multivariate models showed that QoL and erectile function were significantly affected, before surgery, by symptoms and signs that are usually considered as pertaining to the metabolic syndrome, while sexual hormones are essentially correlated to erectile dysfunction., Competing Interests: None

Purpose: PSA is known to be lowered in obese patients. There is a lack of data regarding patients with prostate cancer. Our objective was to prospectively assess the relationship PSA concentration, PSA mass and BMI in a cohort of patients with localized prostate cancer., Methods: A prospective, multicenter cohort study was conducted including patients undergoing radical prostatectomy. Clinical and biological data were collected for each patient before surgery., Results: A total of 1343 patients were analyzed. Mean age was 64.0 years. Mean weight was 82.2 kg and mean BMI was 26.8 kg/m 2 . Mean PSA concentration was 8.7 ng/mL and mean PSA mass 29.3 ng. On univariate analysis, an association was found between PSA mass and either BMI, weight and waist circumference. No association was found between PSA concentration and each weight parameters. On multivariate analysis, obesity was not an independent predictor of PSA concentration (p = 0.73). Independent predictors of PSA concentration were cardiovascular disease (negative association, p = 0.034), predominant Gleason 4 (positive association, p < 0.001) and pT3a (positive association, p < 0.001). BMI was an independent predictor of PSA mass (positive association, p = 0.009). PSA mass was negatively associated with TT (p = 0.015) and cardiovascular disease (p = 0.003), and positively associated with BT (p = 0.032), Gleason grade ≥ 4 + 3 (p < 0.001) and pT3a (p < 0.001)., Conclusion: In this prospective study of patients with localized prostate cancer, higher BMI was associated with higher PSA mass but not with higher PSA concentration. Screening obese patients with a specific PSA method does not appear to be critical., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Robust data evaluating the association of preoperative parameters of the patients with quality of life after radical prostatectomy are lacking. We investigated whether clinical and biological preoperative characteristics of the patients were associated with impaired patient-reported quality of life (QoL) and sexual outcomes 1 year after radical prostatectomy. We evaluated patient-reported outcomes among the 1343 men participating in the AndroCan trial (NCT02235142). QoL and erectile dysfunction (ED) were assessed before and 1 year after radical prostatectomy using validated self-assessment questionnaires (Aging Male's Symptoms [AMS] and the 5-item abridged version of the International Index of Erectile Function [IIEF5]). At baseline, 1194 patients (88.9%) accepted to participate. A total of 750 (55.8%) patients answered the 1-year postoperative questionnaires. Out of them, only 378 (50.4% of responders) provided answers that could be used for calculations. One year after prostatectomy, ED had worsened by 8.0 (95% confidence interval [CI]: 7.3-8.7; P < 0.0001) out of a maximum of 20. The global AMS score has worsened by 2.8 (95% CI: 1.7-3.8; P < 0.0001). ED scores 1 year postsurgery were positively correlated with preoperative age and percentage of fat mass, and negatively correlated with total cholesterol, dehydroepiandrosterone (DHEA), and androstenediol (D5); AMS were poorly correlated with preoperative parameters. QoL and sexual symptoms significantly worsened after radical prostatectomy. Baseline bioavailable testosterone levels were significantly correlated with smaller changes on AMS somatic subscores postprostatectomy. These findings may be used to inform patients with newly diagnosed prostate cancer., Competing Interests: None

A dual-loop controller permits the automated titration of propofol and remifentanil during anesthesia; it has never been used in intensive care after cardiac surgery. The goal of this preliminary study was to determine the efficacy of this controller to provide postoperative sedation in 19 adult cardiac surgery patients with a Bispectral Index target of 50. Results are presented as numbers (percentages) or medians [25th-75th percentiles]. The sedation period lasted 139 min [89-205] during which the Richmond Agitation Sedation Scale was at - 5 and the Behavioral Pain Scale score at three points for all patients and observation times but one (82 out of 83 assessments). Sedation time in the range 40-60 for the Bispectral Index was 87% [57-95]; one patient had a period of electrical silence defined as Suppression Ratio at least > 10% for more than 60 s. The time between the end of infusions and tracheal extubation was 84 min [63-129]. The Richmond Agitation Sedation Scale was 0 [0-0], 0 [- 1 to 0], and 0 [0-0] respectively during the 3 h following extubation while the verbal numerical pain scores were 6 [4.5-7], 5 [4-6], and 2 [0-5]. Mean arterial pressure decreased during sedation requiring therapeutic interventions, mainly vascular filling in 15 (79%) patients. Automated sedation device was discontinued in two patients for hemodynamic instability. No patient had awareness of the postoperative sedation period. Dual closed-loop can provide postoperative sedation after cardiac surgery but the choice of the depth of sedation should take into account the risk of hypotension.

Background: The questionnaire from Ringsted et al. (RQ) assesses the consequences on daily activities of a post-thoracotomy pain syndrome. Our study aimed at translating the RQ into French and to validate its metrological properties., Methods: Four months after thoracotomy, 134 patients participating in a prospective comparative study of two surgical thoracotomy approaches (axillary and posterolateral) scored the translated questionnaire. The sensitivity of this version was assessed by comparing scores from patients complaining of pain to that of non-complainers. Concurrent validity was assessed using ratings from direct questions on pain, mood, anxiety and enjoyment of life. Homogeneity was assessed with Crombach's coefficient and dimensionality with PCA., Results: A scoring system was devised to homogenise pain-related impairment with activities that were never performed before surgery and activities that had to be abandoned due to pain. The French version is bi-dimensional: routine activities (carrying heavy loads, raising the arms above the head, housework, getting out of bed, car driving, lying on the operated side, coughing, sitting for half an hour) are opposed to running, walking 1 km, climbing stairs, bending knees, standing for half an hour, swimming and cycling; both these factors contribute independently to the global score. Global and factor scores are sensitive to presence of pain while direct questions account for 20 to 50 % of the information provided by the questionnaire., Conclusion: The French version of the RQ is suitable to assess chronic repercussions of lung surgery on the ability of patients to perform their daily activities., (Copyright © 2019 Société française d'anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.)

Background: Currently, there is no consensus regarding the expected concentration levels of intra-prostatic sex steroids in patients with Prostate Cancer (PCa). Our objective was to assess the concentration levels of sex steroids in prostatic tissue and serum, in two cohorts of patients with localized PCa or benign prostatic hyperplasia (BPH)., Methods: Between September 2014 and January 2017, men selected for radical cystectomy (for bladder cancer) or open prostatectomy (for BPH), and men selected for radical prostatectomy for localized PCa were included. Blood samples were collected at baseline before surgery, and steroid concentrations were assessed following the recommendations of the Endocrine Society. Intra-prostatic samples were collected from fresh surgical samples, and assessed by gas chromatography and mass spectrometry (GC/MS). Permanova analysis was performed. Analyses were adjusted for age, prostate weight, and prostate-specific antigen (PSA) level., Results: A total of 73 patients (41 patients with PCa and 32 patients with BPH) were included in this study. Patients with PCa were younger, and had smaller prostate volumes with higher levels of PSA. The levels of Total Testosterone (TT), Di-Hydro-Testosterone (DHT), and Estradiol (E2) in the serum were not significantly different between PCa and BPH. In PCa tissue, TT concentrations were significantly lower (0.11 ng/g vs 0.47 ng/g, P = 0.0002), however its derivative E2 had significantly higher concentrations (31.0 ng/g vs 22.3 ng/g, P = 0.01). DHT tissue concentrations were not significantly different between the two groups (5.55 ng/g vs 5.42 ng/g, P = 0.70). Intra-prostatic TT concentrations were significantly lower in the peripheral zone than in the central zone for the CaP group (0.07 ng/g vs 0.15 ng/g, P = 0.004)., Conclusions: Patients with PCa had lower intra-prostatic TT and higher E2 concentrations levels compared to the patients with BPH. PCa seem to consume more TT and produce more E2, especially in the peripheral zone., (© 2018 Wiley Periodicals, Inc.)

Failure rates after first-line treatment of localized prostate cancer (PCa) treatment remain high. Improvements to patient selection and identification of at-risk patients are central to reducing mortality. We aimed to determine if cancer aggressiveness correlates with androgen levels in patients undergoing radical prostatectomy for localized PCa. We performed a prospective, multicenter cohort study between June 2013 and June 2016, involving men with localized PCa scheduled to undergo radical prostatectomy. Clinical and hormonal patient data (testosterone deficiency, defined by total testosterone (TT) levels < 300 ng/dL and/or bioavailable testosterone (BT) levels < 80 ng/dL) were prospectively collected, along with pathological assessment of preoperative biopsy and subsequent radical prostatectomy specimens, using predominant Gleason pattern (prdGP) 3/4 grading. Of 1343 patients analyzed, 912 (68%) had prdGP3 PCa and 431 (32%) had high-grade (prdGP4, i.e., ISUP ≥ 3) disease on prostatectomy specimens. Only moderate concordance in prdGP scores between prostate biopsies and prostatectomy specimens was found. Compared with patients with prdGP3 tumors (i.e., ISUP ≤ 2), significantly more patients with prdGP4 cancers had demonstrable hypogonadism, characterized either by BT levels (17.4% vs. 10.7%, p < 0.001) or TT levels (14.2% vs. 9.7%, p = 0.020). BT levels were also lower in patients with prdGP4 tumors compared to those with prdGP3 disease. Testosterone deficiency (defined by TT and/or BT levels) was independently associated with higher PCa aggressiveness. BT is a predictive factor for prdGP4 disease, and evaluating both TT and BT to define hypogonadism is valuable in preoperative assessment of PCa (AndroCan Trial: NCT02235142).

Background: Transcutaneous electrical nerve stimulation (TENS) is often used for the treatment of low-back pain (LBP). However, its effectiveness is controversial., Objective: To determine the efficacy of TENS in the treatment LBP when associated to a therapeutic education program (TEP)., Design: Open randomized monocentric study., Setting: University hospital between 2010 and 2014., Patients: A total of 97 patients suffering from LBP., Interventions: Routine care (TENS group) or routine care plus a therapeutic education program (TENS-TEP group) based on consultation support by a pain resource nurse., Main Outcome Measures: EIFEL and Dallas Pain Questionnaire scores., Results: Twenty-two patients (44%) were still assessable at the end-of-study visit, whereas 33 (70%) were assessable at the same time point in the TENS-TEP group (P = .013). The EIFEL score and the Dallas score had a similar evolution over time between groups (P = .18 and P = .50 respectively). Similarly, there were no significant differences between the groups with respect to resting pain scores (P = .94 for back pain and P = .16 for leg pain) and movement pain scores (P = .52 for back pain and P = .56 for leg pain). At Month 6, there was no significant difference between the groups (P = .85) with regard to analgesics and social impact. Two patients presented a serious adverse event during the study (one in each group) but non-attributable to the treatment studied., Conclusion: This study does not support the use of TENS in the treatment of patients with chronic LBP even though patients benefited from a therapeutic education program by a pain resource nurse. However, the higher number of premature withdrawals in the TENS group may be due to early withdrawal of patients who did not experience improvement of their symptoms.

Background: The specific involvement of the sex steroids in the growth of the prostatic tissue remains unclear. Sex steroid concentrations in plasma and in fresh surgical samples of benign central prostate were correlated to prostate volume., Methods: Monocentric prospective study performed between September 2014 and January 2017. Age, obesity parameters, and both serum and intraprostatic concentrations of sex steroids were collected complying with the latest Endocrine Society guidelines and the steroids assessed by GC/MS. Statistical calculations were adjusted for age and body mass index (BMI)., Results: Thirty-two patients, equally divided between normal- and high-volume prostate groups, were included in the analysis. High-volume prostate patients were older, heavier and had higher BMI. Comparison adjusted for age and BMI showed higher DHT concentrations in high-volume prostate. Both normal- and high-volume prostate tissues concentrate sex steroids in a similar way. Comparison of enzymatic activity surrogate marker ratios within tissue highlighted similar TT/E1 and TT/E2 ratios, and higher DHT/E1 ratio and lower DHT/PSA ratio in the high-volume prostates., Conclusions: STERPROSER trial provides evidence for higher DHT concentration in highvolume prostates, that could reflect either higher 5-alpha reductase expression or lower expression of downstream metabolizing enzymes such as 3a-hydoxysteroid dehydrogenase., (© 2017 Wiley Periodicals, Inc.)

Background: Decrease of the nociceptive stimulation induced by laryngoscopy could be an advantage for patients without risk of difficult intubation. The present study aimed to compare the difference in nociceptive stimulation between the use of a conventional laryngoscope or of a videolaryngoscope. Amount of nociception was assessed indirectly using the peak remifentanil concentration determined by a closed-loop administration of propofol and remifentanil with bispectral index (BIS) as the input signal (target 50)., Methods: A prospective single-center randomized study was performed including surgical patients without predictable risk of difficult mask ventilation or of difficult tracheal intubation. Forty consecutive surgery patients were randomly assigned to CL group (conventional laryngoscope) or VL group (McGrath Mac videolaryngoscope). Induction of anesthesia was performed automatically using the closed-loop system and myorelaxation with atracurium. The allocation was revealed just before tracheal intubation. The primary outcome was the peak plasma remifentanil concentration observed during the 5-minute period which followed intubation., Results: Sixteen patients in the CL group and 11 in the VL group were analyzed. Plasmatic remifentanil and propofol concentrations were similar in both groups either before tracheal intubation or during the 5 minutes following intubation. There was a nonsignificant between-group difference (P = .09) for the peak concentration of remifentanil. A comparable result was observed for other outcomes except for the heart rate which increased in the CL group., Conclusion: Use of the videolaryngoscope McGrath Mac did not reduce the nociceptive stimulation induced during intubation as evaluated by the automatically administered remifentanil concentration., Trial Registration: ClinicalTrials.gov, NCT02245789.

Background: We reviewed our experience with tracheal extubation in the operating room (E-OR) among cystic fibrosis patients requiring bilateral lung transplantation to evaluate safety and determine predictive factors of E-OR., Methods: The charts of 89 recipients (from May 2007 to June 2013) were analysed. Patients were divided into E-OR and E-ICU (intensive care unit extubation) groups. Data are expressed as numbers (percentages) or medians [25th-75th percentiles]., Results: There were 41 patients in the E-OR group (46%). Donor and recipient characteristics were similar between groups. Intraoperative complications occurred less frequently in the E-OR group, and fluid and transfusion requirements were lower. Postoperative courses were different in the E-OR group, including a lower rate of grade 3 primary graft dysfunction (0 compared with 19 patients, P<0.0001) and shorter ICU (5.0 [3.7-7.2] compared with 11.5 [7.0-15.5] days) and hospital stays (22.0 [18.0-25.5] compared with 33.0 [25.0-56.5] days, respectively; P<0.0001 for both). The 1 yr survival rates were similar: 95% in the E-OR group and 98% in the E-ICU group. A statistical model built on a development cohort of 60 randomly selected patients predicted 95% of E-OR instances in this cohort and 82% of E-OR instances in the validation cohort (28 patients). Predictive factors were complications during single-lung ventilation (second graft implantation), complications during bipulmonary ventilation (end of surgery), and the ratio of arterial partial pressure of oxygen to fractional inspired oxygen (end of surgery)., Conclusions: Our protocol allowed for extubation of 46% of bilateral lung transplant patients without increased postoperative risks., (© The Author 2016. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: A rehabilitation program, a multimodal strategy favoring rapid postoperative return to autonomy, has rarely been undertaken after thoracic surgery compared to colectomy. The primary outcome of this fast-track program was the length of postoperative stay. Secondary outcomes concerned the feasibility of this strategy, the incidence of postoperative complications and 3-month postoperative mortality., Methods: Patients were included in this prospective single-center observational study if they were scheduled for lung resection (lobectomy or wedge resection) performed by posterolateral thoracotomy. The rehabilitation program, coordinated by a referent nurse, included a list of actions to be done, especially early feeding and ambulation, multimodal analgesia including epidural analgesia, early removal of chest tube., Results: One hundred and two patients were included in total with two exclusions (failure of epidural analgesia). The postoperative hospital stay was 8 (7-10) days (median [25-75th percentiles]); this duration was similar to that of the historical cohort which was 9 [7-13] days (P=0.06). Most actions were conducted with a high level of acceptance except for the insertion of a single chest tube (19%) and its removal later than expected in the program. Only 50% of patients left hospital shortly after exit criteria were met suggesting failure in the organization. Patients' satisfaction rate reached 77% and no postoperative death was reported during the follow-up period., Conclusion: A program for early rehabilitation is feasible after thoracotomy. Chest drainage and organization to optimize the length of stay are crucial points.

International Normalized Ratio (INR) is currently used to monitor vitamin K antagonist therapy, and the bleeding incidence becomes exponential for INR>4.5. Inversely, more than 50% of patients with a supratherapeutic INR are asymptomatic. Therefore it could be of interest to identify patients with a higher bleeding risk. Microparticles derived from different cell types express procoagulant phospholipids (PPL) which can be evaluated by a chronometric coagulation assay where a shortening of the clotting times is associated with increased levels of PPL. In a series of 174 consecutive patients referred to our Emergency Department with an INR>5, median level of PPL was significantly (p=0.004) lower (38.2s) in the 119 asymptomatic patients than in patients with nonmajor (43.6s, n=35) or major bleeding (46.6s, n=19), indicating higher levels of procoagulant phospholipids in asymptomatic patients. By receiver operating characteristic curve analysis, a cut-off of 43.5s discriminated patients with higher haemorrhagic risk (area under the curve=0.648). In contrast, thrombomodulin levels, quantified either by immunological or functional assays were not significantly different between both groups. In conclusion, evaluation of PPL could be of interest to define the haemorrhagic risk of VKA- treated patients., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Introduction: Reconstruction of the oral cavity and oropharynx after tumour resection often involves the use of free flaps, but donor site morbidity must be taken into account. The radial forearm flap, the flap most commonly used in this setting, leaves a readily visible scar on an exposed region of the body. The thoracodorsal artery perforator flap (TDAP), which possesses the same plastic qualities as the radial forearm flap, leaves a scar that is hidden in the axilla. The purpose of this study was to evaluate the cosmetic results of radial forearm and thoracodorsal artery perforator free flap donor sites., Material and Methods: The medical charts of all patients undergoing reconstruction by a radial forearm or thoracodorsal artery perforator free flap between January 2011 and December 2011 were retrospectively reviewed. The Patient and Observer Scar Assessment Scales and the Vancouver Scar Scale were used to evaluate the quality of the scars., Results: Reconstruction was performed by radial forearm flap in 4 cases and TDAP flap in 7 cases. The PSAS score was significantly lower in the TDAP group than in the radial forearm group (P=0.03), and the OSAS score was higher in the radial forearm group (21.5 versus 14). The Vancouver Scar Scale was significantly higher for radial forearm flap scars than for TDAP scars (8 versus 2.7, P=0.005)., Conclusion: This is the first study to compare radial forearm and thoracodorsal artery perforator free flap donor site scars. It demonstrates the minimal TDAP donor site morbidity and the high level of patient satisfaction., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Chronic granulomatous disease (CGD) is a primary immunodeficiency caused by failure of superoxide production in phagocytic cells. The disease is characterised by recurrent infections and inflammatory events, frequently affecting the lungs. Improvement of life expectancy now allows most patients to reach adulthood. We aimed to describe the pattern of pulmonary manifestations occurring during adulthood in CGD patients. This was a retrospective study of the French national cohort of adult patients (≥16 years old) with CGD. Medical data were obtained for 67 adult patients. Pulmonary manifestations affected two-thirds of adult patients. Their incidence was significantly higher than in childhood (mean annual rate 0.22 versus 0.07, p=0.01). Infectious risk persisted despite anti-infectious prophylaxis. Invasive fungal infections were frequent (0.11 per year per patient) and asymptomatic in 37% of the cases. They often required lung biopsy for diagnosis (10 out of 30). Noninfectious respiratory events concerned 28% of adult patients, frequently associated with a concomitant fungal infection (40%). They were more frequent in patients with the X-linked form of CGD. Immune-modulator therapies were required in most cases (70%). Respiratory manifestations are major complications of CGD in adulthood. Noninfectious pulmonary manifestations are as deleterious as infectious pneumonia. A specific respiratory monitoring is necessary., (Copyright ©ERS 2015.)

Background: Left double-lumen tracheal tubes (DLTs), with or without a hook to engage the carina, remain the standard device for lung isolation during anaesthesia., Objective: The purpose of the study was to compare these DLTs with and without a hook., Design: A randomised, controlled, single-blinded study., Setting: University hospital., Participants: One hundred and eighty-four patients undergoing lung resection., Main Outcome Measure: Time required to position the tube from the introduction of the tube into the mouth to confirmation of correct placement in the supine position., Results: Baseline characteristics were well balanced between the groups. Time to place DLTs was similar in both groups: median (interquartile range, IQR) 81.0 (50.0 to 146.2) s for DLTs without a hook and 67.5 s (45.0 to 138.7) for DLTs with a hook (P = 0.43). The incidence of adequate position at the first attempt was 68.5% in the No hook group and 69.6% in the Hook group (P = 0.95). Patients in both groups suffered similar incidences of sore throat at day 0 and day 1 (P = 0.80 and P = 0.20, respectively). No major lesion of the vocal cords or tracheobronchial tree was discovered and the incidence of minor lesions was similar in both groups., Conclusion: When a DLT is used, the presence of a carinal hook gives neither advantage nor added complications., Trial Registration: ClinicalTrials.gov, NCT00969683.

Background: In acute ischemic stroke (AIS), bridging therapy, including intravenous thrombolysis (IVT) and mechanical thrombectomy (MET), appears to be very promising. However, data on the impact of IVT before the endovascular procedure are limited., Methods: To examine the impact of IVT on the MET procedure, we compared the duration of this procedure, number of passes, recanalization rate, safety issues, and outcome in consecutively recruited patients either eligible for MET alone (intravenous fibrinolysis contraindication) or receiving MET preceded by IVT for proximal middle cerebral artery (MCA) occlusion within 6 hours of stroke onset., Results: From January 2011 to June 2013, 68 cases with proximal MCA occlusion were available for analysis (MET alone, 40; IVT + MET, 28). The 2 groups did not differ significantly in baseline characteristics. The median National Institutes of Health Stroke Scale score at admission was 15 (10-20) for MET and 18 (13-19) for IVT + MET groups, respectively (P = .39). The median duration of the endovascular procedure (from groin puncture to recanalization) was significantly shorter in the IVT + MET group compared with that in MET alone (35 minutes [21-60] versus 60 minutes [25-91]; P = .043). The number of passes of the thrombectomy device per patient tended to be lower in the IVT + MET group than those in the MET group (P = .080). The IVT + MET group also had a higher rate of complete recanalization and a better outcome at 3 months., Conclusions: Prior IVT may facilitate the MET procedure. Further studies on MET in AIS should assess the direct impact of IVT on the endovascular procedure., (Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Context: Pain in patients awaiting lung transplantation is not well known., Objectives: This study prospectively investigated prevalence and characteristics of pain in these patients., Methods: Assessment, undertaken at the time of registration, comprised an interview, a physical examination by a pain-qualified anesthesiologist, and a questionnaire completed by the patient and investigator. This questionnaire included evaluation of pain (intensity, location, sensory and affective qualifications, and treatment), detection of neuropathic pain, and assessment of anxiety and depression. A patient was considered "with pain" when at least one of the following criteria was met: 1) positive answer to the question "Do you suffer regularly from pain?" and 2) score greater than 3 on at least one of three numeric pain scales (current, maximal, and average during the last eight days) ranging from 0 (no pain) to 10 (most severe pain imaginable)., Results: One hundred forty-three patients were enrolled. Prevalence of pain was 59%. Three independent variables were correlated to the magnitude of the average pain score for the preceding eight days: female gender (P = 0.003), cystic fibrosis (P = 0.02), and depression score (P = 0.02). Among the pain patients, 39% took analgesic drugs daily and 36% regularly but less than daily; 2% used opioids. Nineteen percent used nonpharmacological strategies (e.g., hypnosis, relaxation)., Conclusion: This study highlights the prevalence of pain in this population and specific problems associated with pain such as anxiety and depression. Appropriate assessment and treatment of pain should be considered a component of pretransplantation management., (Copyright © 2015 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Background: The minimally important difference (MID) has been defined as the smallest improvement considered worthwhile by a patient. The MID has not been estimated for the Rhinoconjunctivitis Total Symptom Score (RTSS)., Methods: In a prospective multicentre study, patients consulting for grass-pollen-induced allergic rhinitis (AR) recorded a 15-point global rating of change scale (GRCS) score and the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) score on a weekly basis and the individual symptom scores comprising the RTSS on a daily basis over two consecutive weeks. The MID in the RTSS was determined with anchor-based methods (using the GRCS and the RQLQ) and a distribution-based method [based on the RTSS' standard deviation (SD)]., Results: The study population comprised 806 patients (253 children, 250 adolescents and 303 adults). During the first week of the study, the mean ± SD RTSSs for these age groups were 6.5 ± 3.3, 6.8 ± 3.4 and 7.0 ± 3.4, respectively. For an improvement of 2 points in the GRCS or 0.5 points in the RQLQ score, the regression analysis yielded MIDs in the RTSS of 1.24 ± 0.17 and 1.12 ± 0.14 in children, 1.33 ± 0.14 and 1.20 ± 0.13 in adolescents and 1.13 ± 0.14 and 0.89 ± 0.12 in adults, respectively. When applying distribution-based methods, the MID ranged from 1.09 to 1.13 (based on 0.33 SDs of the first-week RTSS) and from 1.22 to 1.40 (based on 0.5 SDs of the difference in RTSSs between the first and second weeks)., Conclusion: The MID in the RTSS was consistently estimated as 1.1-1.3 (and could conceivably be rounded to 1) in patients with grass-pollen-induced AR., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: In accordance with the European Association of Urology guidelines, a second transurethral resection of the bladder (TURB) is recommended for high-grade or T1-category tumors. This practice brings into question the benefit of photodynamic diagnosis (PDD) in reducing the residual disease after TURB in patients with positive results on urine cytology showing high-grade cancer cells., Methods and Materials: A prospective, bicentric, randomized study comparing white light cystoscopy (WLC)+PDD with hexaminolevulinate arm with WLC alone (control arm) during the first TURB in patients with primary non-muscle-invasive bladder cancer and with positive results on urine cytology showing high-grade cancer cells. Patients underwent a first TURB with WLC and PDD or WLC alone, and then a second TURB with WLC and PDD, after 4 to 6 weeks. The number of tumors visualized in WLC and PDD and histology of the TURB specimen was recorded to perform a statistical analysis comparing both the 2 arms., Results: A total of 151 patients were enrolled (hexaminolevulinate, n = 72; control, n = 79). The number of visualized tumors did not increase with PDD in the first or second TURB. During the second TURB, the residual tumor rate was not reduced in patients who had PDD during the first TURB. No significant difference was observed regarding the pattern of category and grade, the size, and the recurrence and progression risks during either the first or the second TURB., Conclusions: In the setting of primary non-muscle-invasive bladder cancer with positive results on urine cytology, performing a second TURB allows to diagnose residual tumor in approximately half of the cases. This rate was not significantly reduced by the use of the PDD during the first TURB., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: To compare the analgesic effect of ultrasound-guided Transversus Abdominis Plane (TAP) block versus Continuous Wound Infusion (CWI) with levobupivacaine after caesarean delivery., Methods: We recruited parturients undergoing elective caesareans for this multicenter study. Following written informed consent, they received a spinal anaesthetic without intrathecal morphine for their caesarean section. The postoperative analgesia was randomized to either a bilateral ultrasound guided TAP block (levobupivicaine = 150 mg) or a CWI through an elastomeric pump for 48 hours (levobupivacaine = 150 mg the first day and 12.5 mg/h thereafter). Every woman received regular analgesics along with oral morphine if required. The primary outcome was comparison of the 48-hour area under the curve (AUC) pain scores. Secondary outcomes included morphine consumption, adverse events, and persistent pain one month postoperatively., Results: Recruitment of 120 women was planned but the study was prematurely terminated due to the occurrence of generalized seizures in one patient of the TAP group. By then, 36 patients with TAP and 29 with CWI had completed the study. AUC of pain at rest and during mobilization were not significantly different: 50 [22.5-80] in TAP versus 50 [27.5-130] in CWI (P = 0.4) and 190 [130-240] versus 160 [112.5-247.5] (P = 0.5), respectively. Morphine consumption (0 [0-20] mg in the TAP group and 10 [0-32.5] mg in the CWI group (P = 0.09)) and persistent pain at one month were similar in both groups (respectively 29.6% and 26.6% (P = 0.73))., Conclusion: In cases of morphine-free spinal anesthesia for cesarean delivery, no difference between TAP block and CWI for postoperative analgesia was suggested. TAP block may induce seizures in this specific context. Consequently, such a technique after a caesarean section cannot be recommended., Trial Registration: ClinicalTrials.gov NCT01151943.

Objectives: In the emergency department (ED), intravenous (IV) catheter placement is one of the most frequent interventions and may be a real challenge in some conditions. Improvement of the success rate with new technology represents a great opportunity. This randomized controlled trial aimed to show the superiority of AccuVein to cannulate veins in adults compared to routine care., Methods: After giving written consent, patients were randomized into two groups: routine IV catheter insertion or insertion guided by the AccuVein, which is a hand-held instrument displaying laser light to optimize visualization of veins. The primary outcome was the time to successful placement of catheters. Secondary outcomes included the number of attempts, the rate of failure, technique-related pain, occurrence of movements, and efficiency of IV cannulation as perceived by the operator when using the AccuVein device. Results are given as mean and bootstrapped 95% confidence interval (CI) and percentages. p-values of <0.05 were considered significant., Results: A total of 266 six patients were included, with 157 randomized to routine cannulation and 115 to AccuVein. Patient characteristics were similar. Time to successful placement of IV catheter (routine, 98 seconds, 95% CI = 85 to 113 seconds; and AccuVein, 119 seconds, 95% CI = 93 to 154 seconds) was not different between groups (p = 0.24). Secondary outcomes (failure and pain) did not significantly differ, except for movements, which were more frequent when using the AccuVein device (19.1% vs. 10.2%, p = 0.05). Evaluation of the AccuVein by operators was more often negative than positive., Conclusions: Use of the AccuVein did not improve IV cannulation in nonselected ED patients., (© 2014 by the Society for Academic Emergency Medicine.)

Background: The capacity of sublingual allergen immunotherapy (SLIT) to provide effective symptom relief in pollen-induced seasonal allergic rhinitis is often questioned, despite evidence of clinical efficacy from meta-analyses and well-powered, double-blind, placebo-controlled randomized clinical trials. In the absence of direct, head-to-head, comparative trials of SLIT and symptomatic medication, only indirect comparisons are possible., Methods: We performed a meta-analysis of classes of products (second-generation H1-antihistamines, nasal corticosteroids and grass pollen SLIT tablet formulations) and single products (the azelastine-fluticasone combination MP29-02, and the leukotriene receptor antagonist montelukast) for the treatment of seasonal allergic rhinitis in adults, adolescents and/or children. We searched the literature for large (n >100 in the smallest treatment arm) double-blind, placebo-controlled randomized clinical trials. For each drug or drug class, we performed a meta-analysis of the effect on symptom scores. For each selected trial, we calculated the relative clinical impact (according to a previously published method) on the basis of the reported post-treatment or season-long nasal or total symptom scores: 100 × (scorePlacebo - scoreActive)/scorePlacebo., Results: Twenty-eight publications on symptomatic medication trials and ten on SLIT trials met our selection criteria (total number of patients: n = 21,223). The Hedges' g values from the meta-analyses confirmed the presence of a treatment effect for all drug classes. In an indirect comparison, the weighted mean (range) relative clinical impacts were -29.6% (-23% to -37%) for five-grass pollen SLIT tablets, -19.2% (-6% to -29%) for timothy pollen SLIT tablets, -23.5% (-7% to -54%) for nasal corticosteroids, -17.1% (-15% to -20%) for MP29-02, -15.0% (-3% to -26%) for H1-antihistamines and -6.5% (-3% to -10%) for montelukast., Conclusions: In an indirect comparison, grass pollen SLIT tablets had a greater mean relative clinical impact than second-generation antihistamines and montelukast and much the same mean relative clinical impact as nasal corticosteroids. This result was obtained despite the presence of methodological factors that mask the clinical efficacy of SLIT for the treatment of seasonal allergic rhinitis.

Background: The optimal dose of tranexamic acid (TA) is still an issue. The authors compared two doses of TA during cardiac surgery in a multicenter, double-blinded, randomized study., Methods: Patients were stratified according to transfusion risk, then randomized to two TA doses: 10 mg/kg bolus followed by 1 mg·kg·h infusion (low dose) until the end of surgery or 30 mg/kg bolus followed by 16 mg·kg·h infusion (high dose). The primary endpoint was the incidence of blood product transfusion up to day 7. Secondary ones were incidences of transfusion for each type of blood product and amounts transfused, blood loss, repeat surgery, TA-related adverse events, and mortality., Results: The low-dose group comprised 284 patients and the high-dose one 285. The primary endpoint was not significantly different between TA doses (63% for low dose vs. 60% for high dose; P = 0.3). With the high dose, a lower incidence of frozen plasma (18 vs. 26%; P = 0.03) and platelet concentrate (15 vs. 23%; P = 0.02) transfusions, lower amounts of blood products (2.5 ± 0.38 vs. 4.1 ± 0.39; P = 0.02), fresh frozen plasma (0.49 ± 0.14 vs.1.07 ± 0.14; P = 0.02), and platelet concentrates transfused (0.50 ± 0.15 vs. 1.13 ± 0.15; P = 0.02), lower blood loss (590 ± 50.4 vs. 820 ± 50.7; P = 0.01), and less repeat surgery (2.5 vs. 6%; P = 0.01) were observed. These results are more marked in patients with a high risk for transfusion., Conclusions: A high dose of TA does not reduce incidence of blood product transfusion up to day 7, but is more effective than a low dose to decrease transfusion needs, blood loss, and repeat surgery.

Background: Several commercial formulations of propofol are available. The primary outcome of this study was the required dose of propofol alone or combined with lidocaine to achieve induction of general anesthesia., Methods: This multicenter, double-blinded trial randomized patients (American Society of Anesthesiologists physical status I-III) just before elective surgery with the use of a computer-generated list. Three different propofol 1% formulations-Diprivan (Astra-Zeneca, Cheshire, United Kingdom), Propoven (Fresenius-Kabi AG, Bad Homburg, Germany), and Lipuro (B-Braun, Melshungen AG, Germany)-were compared with either placebo (saline solution) or lidocaine 1% mixed to the propofol solution. Depth of anesthesia was automatically guided by bispectral index and by a computerized closed-loop system for induction, thus avoiding dosing bias. The authors recorded the total dose of propofol and duration of induction and the patient's discomfort through a behavioral scale (facial expression, verbal response, and arm withdrawal) ranging from 0 to 6. The authors further evaluated postoperative recall of pain using a Visual Analog Scale., Results: Of the 227 patients enrolled, 217 were available for analysis. Demographic characteristics were similar in each group. Propoven required a higher dose for induction (2.2 ± 0.1 mg/kg) than Diprivan (1.8 ± 0.1 mg/kg) or Lipuro (1.7 ± 0.1 mg/kg; P = 0.02). However, induction doses were similar when propofol formulations were mixed with lidocaine. Patient discomfort during injection was significantly reduced with lidocaine for every formulation: Diprivan (0.5 ± 0.3 vs. 2.3 ± 0.3), Propoven (0.4 ± 0.3 vs. 2.4 ± 0.3), and Lipuro (1.1 ± 0.3 vs. 1.4 ± 0.3), all differences significant, with P < 0.0001. No adverse effect was reported., Conclusion: Plain propofol formulations are not equipotent, but comparable doses were required when lidocaine was concomitantly administered.

Brain contains large amounts of tissue factor, the major initiator of the coagulation cascade. Neuronal apoptosis after intracerebral haemorrhage (ICH) leads to the shedding of procoagulant phospholipids (PPLs). The aim of this study was to investigate the generation of PPL, tissue factor activity (TFa), and D-Dimer (D-Di) in the cerebrospinal fluid (CSF) at the acute phase of ICH in comparison with other brain diseases and to examine the relationship between these factors and the outcome of ICH. CSF was collected from 112 patients within 48 hours of hospital admission. Thirty-one patients with no neurological or biochemical abnormalities were used to establish reference range in the CSF ("controls"). Thirty had suffered an ICH, and 51 other neurological diagnoses [12: ventricular drainage following brain surgery, 13: viral meningitis, 15: bacterial meningitis, and 11 a neurodegenerative disease (NDD)]. PPL was measured using a factor Xa-based coagulation assay and TFa by one home test. PPL, D-Di, and TFa were significantly higher (P < 0.001) in the CSF of patients with ICH than in controls. TFa levels were significantly (P < 0.05) higher in ICH than in patients with meningitides or NDD. Higher levels (P < 0.05) of TFa were observed in patients with ICH who died than in survivors. TFa measurement in the CSF of patients with ICH could constitute a new prognostic marker.

Introduction: Angle closure glaucoma, a recognized major world health issue disproportionately affecting women and Asians, is not often considered in our European populations, normotensive subjects, myopic patients, or subjects with a deep anterior chamber. Early diagnosis is worthwhile, as laser peripheral iridotomy (LPI) is an effective one-step treatment of the causal mechanism., Patients and Methods: We have performed a retrospective study of patients who underwent an LPI, the indication for which was based on "photodynamic" gonioscopy in a darkened room showing iridotrabecular contact in darkness. Such photodynamic gonioscopy was motivated by the presence of even minute defects in the nerve fiber layer as seen on the GDxVCC or the presence of a Van Herick sign (narrow limbal anterior chamber depth)., Results: One hundred and three eyes of 103 patients underwent LPI and a minimum 1-year follow-up (mean follow-up almost 2 years). Mean age was 63.7±11.8 years, and women accounted for 63.1% of cases. The vast majority (78.6%) of patients had neither glaucoma nor ocular hypertension. There were 60.1% hyperopes and 39.9% myopes. Over half (57%) had a deep or a very deep anterior chamber. After LPI, there was immediate deepening of the limbal depth of the anterior chamber in 100% of cases. The aqueous humor that flowed forward was almost always viscous-looking. After 1 year, the IOP was 1.3mm Hg±2.4 lower (P<.001) (t test). All patients who had experienced morning headaches (44% of patients) were relieved of this symptom. GDxVCC after 1 year was clearly improved in 18% of cases, slightly improved in 20%, stable in 50%, slightly worse in 11% of cases, and clearly worse in 1%. Cases treated at an earlier stage had a better improvement in GDxVCC., Discussion: Our study shows frequent chronic angle closure in our European population even with deep anterior chambers. Absence of a Van Herick sign does not rule out angle closure at night. A photodynamic gonioscopy with the Goldmann three-lens mirror (to avoid unintentional indentation with the small diameter lenses in these normotensive eyes) should be performed in a darkened room. LPI is an effective one-step treatment of the underlying cause, that is particularly beneficial if performed early., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Background: Metabolic disorders, in particular weight gain, increase cardiovascular mortality risk and can cause serious problems after renal transplantation. Weight and body mass index are imprecise indicators of nutritional status. Accurate determination of the body composition of renal transplant patients is essential; therefore, a simple tool that allows appropriate patient monitoring is crucial., Design: A new device, the Body Composition Monitor (BCM, Fresenius Medical Care, Bad Homburg, Germany), expresses body weight in terms of adipose tissue, lean tissue mass, and excess fluid. We compared the performance of this 3-compartment model with dual-energy X-ray absorptiometry (DEXA) as a reference method in determining body composition in a renal transplant population., Subjects: Thirty-three clinically stable renal transplant patients were studied. Bland-Altman plots and Passing-Bablok regression were used to compare methods., Results: Mean lean mass was 51.8 ± 12.3 kg with DEXA and 39.0 ± 9.9 kg with BCM. Despite the Passing-Bablok regression failing to find significant differences, the predictive value of BCM for DEXA was poor. Mean fat mass was 19.4 ± 9.7 kg with DEXA and 30.0 ± 16.0 kg with BCM. The slope of the regression line of BCM over DEXA significantly differed from 1., Conclusion: We conclude that, in this population, these methods cannot be substituted for one another., (Copyright © 2013 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Multiple organ dysfunction syndrome (MODS) observed in patients with sepsis and in nonseptic patients organ failure (OF) is associated with a high mortality rate. We investigated whether new coagulation assays [quantification of procoagulant phospholipids (PPL) activity, functional assays measuring the activity of thrombomodulin (TMa) or tissue factor (TFa) and thrombin generation using calibrated automated thrombography (CAT)] could constitute new tools to better understand the physiopathology of MODS and have any prognostic value., Methods: We measured TMa, TFa, PPL and CAT in 32 healthy controls, 24 patients with sepsis and 26 patients with non-septic OF. We compared these parameters with usual coagulation assays [prothrombin time, activated partial thromboplastin time, protein C (PC), protein S, D-Dimers (D-Di), soluble thrombomodulin (sTM)] and markers of inflammation (IL-6, CRP). Samples were collected within 24 h of the diagnosis., Results: TMa, TFa, PPL, the lag time and time to thrombin peak levels were increased in both groups of patients. For both groups D-Di, IL-6, CRP and endogenous thrombin potential (ETP) were higher in non-survivors than in survivors, while PC and PPL were lower in non-survivors than in survivors. TMa increase was more marked in non-survivors patients with OF, while the ratio TMa/sTM was low in non-survivors with sepsis. Received operating characteristic (ROC) curve analysis indicated that thrombin peak and ETP were the more powerful discriminating factors in patients with sepsis or non-septic OF, respectively., Conclusions: PPL, TMa and CAT assays could represent promising tools to identify patients with increased risk of mortality in MODS and could procure insights into pathogenesis of MODS.

Background: Ultrasound-guided perineural peripheral nerve block using a hydrodissection technique may reduce the risk of accidental intravascular local anesthetic (LA) injection. In this prospective randomized double-blind study, we tested the hypothesis that median nerve block effectiveness is not reduced when circumferential perineural hydrodissection with dextrose 5% in water (D5W) precedes LA injection., Methods: Patients scheduled for hand surgery were randomized to receive an ultrasound-guided median nerve block at the elbow to achieve circumferential perineural spread with either 6 mL of D5W followed by 6 mL of LA (lidocaine 1.5% with epinephrine 1:200,000) (D5W-LA group) or with 6 mL of LA alone (LA group). The primary outcome was onset time of successful anesthesia defined by a complete abolition of light touch sensation for the index finger., Results: Data from 95 patients were analyzed: 43 in the D5W-LA group and 52 in the LA group. Noninferiority tests were significant (all P < 0.05) for a critical limit of 7 minutes between D5W-LA and LA groups for onset time of the primary criterion, light touch block at index finger (mean ± SD, respectively: 23.9 ± 7.4 and 22.0 ± 7.9 minutes; 95% confidence interval [CI], -5.9 to 2.1 minutes), and for cold block at index fingertip, sensory blocks at thenar eminence, and motor block. Success rate at 30 minutes (defined as complete abolition for cold and light touch at index finger) was noted in 100% and 98.1% (95% CI, -6% to 10%) and 95.2% and 96.2% (95% CI, -13% to 9%) of patients for the D5W-LA and the LA groups., Conclusion: Performing an ultrasound-guided perineural circumferential hydrodissection with D5W into which LA is injected leaves nerve block outcome unchanged. The assumption that this procedure may reduce the risk of intravascular injection and systemic toxicity remains to be demonstrated.

Background: Strongly marked ideological positions on the impact of palliative care and limited hard data plague the debate on physician-assisted death., Methods: A national cross-sectional study on the requests to hasten death (RHD) was conducted among 789 French palliative care organisations. Data were collected for all patients with RHD encountered during year 2010. Data on patients' characteristics, medical, psychological and social context, symptoms, nature of palliative management, patient's evolution and palliative care team's interpretation of the request were obtained., Findings: A majority of centres responded and 342 teams provided descriptions of 783 RHD, 476 by a patient, 258 by relatives or close friends and 49 by the nursing staff. Cancer was the most frequent pathology (72%) and 68% of the patients had entered terminal stage. Patients rarely appeared with uncontrolled pain (3.7%), but had difficulties with feeding (65%), moving (54%), excretion (49%), or were cachectic (39%); 31% were considered to be anxio-depressive; 79% did not give physical reasons for their request; 37% of RHD were maintained and 24% fluctuated despite provision of regular follow-up by a palliative care team to 83% of all cases; 68% of patients died within a month; the interpretation of RHD by the staff was a wish for relief (69%), patient's inextricable situation (44%), actual desire not to continue living (36%) or to be helped to die (30%)., Interpretation: The large number of described cases provides, for the first time, comprehensive hard data on the evolution of RHDs in a country that has not legalised euthanasia. Whatever the way RHD are expressed, they are frequently maintained despite adequate palliative care with suitable control of pain and psychological support by specialists., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: The increasing use of immunosuppressive and cytotoxic therapies leads to a growing number of opportunistic infections especially Pneumocystis jirovecii pneumonia (PCP). The purpose of our study was to describe the population involved, and to assess clinical, biological, and mortality data., Methods: We collected retrospectively the whole medical file of all PCP cases diagnosed in non-HIV infected patients, in two French University Hospitals in the last decade (1999-2009). Diagnosis was made on standard coloration and/or immunofluorescence analysis of bronchoalveolar lavage fluid (BAL)., Results: Forty-one patients were included in the study, mean age 56 (±12.5) years, sex ratio 0.71 men/woman. Underlying diseases were as follow: 12 patients (29%) were renal transplant recipients, 13 (32%) were treated for solid cancers, and 16 (39%) suffered from various diseases (three allogenic bone-marrow transplantation, 11 hematological malignancies, one pulmonary transplantation, one vasculitis). Twelve patients died (i.e. 29%). Median lymphocyte count was 542/mm(3). More than 85% patients received corticosteroids at a median cumulative 6-month dose of 2700mg. Seven patients (17%) had a PCP prophylaxis. Clinical worsening at day 5 (P<0.003), poor control of the underlying disease (P<0.015), WHO performans status superior than 2 (P<0.025), high temperature (P<0.04), and high oxygen flow (P<0.042) were linked to a poor prognosis., Discussion/conclusion: The prognosis factors found are mostly linked to the patients' clinical severity. We would like to highlight: first, near to 30% mortality rate, secondly, a lack of prophylaxis in 34 patients, reflecting the difficulty to define PCP's risk in non HIV-infected patients., (2011 Elsevier Masson SAS. All rights reserved.)

Study Objective: Hemoglobin measurement is a routine procedure, and a noninvasive point-of-care device may increase the quality of care. The aim of the present study is to compare hemoglobin concentration values obtained with a portable totally noninvasive device, the Masimo Labs Radical-7 Pulse CO-Oximeter, with the results obtained by the ADVIA 2120 in the laboratory., Methods: This was a prospective monocentric open trial enrolling patients consulting in the emergency department of a university hospital from June 16 to December 17, 2009. The main outcome measure was the agreement between both methods and evaluation of the percentage of potential decision error for transfusion., Results: Samples from 300 consecutive patients were assessed. Hemoglobin concentration could not be obtained with the new device for 24 patients. In others, the mean bias, the lower and the upper limits of agreement between the 2 methods, was 1.8 g/dL (95% estimated confidence interval [CI] 1.5 to 2.1 g/dL), -3.3 g/dL (95% CI -3.8 to -2.8 g/dL), and 6.9 g/dL (95% CI 6.4 to 7.4 g/dL), respectively. The intraclass correlation coefficient was 0.53 (estimated 95% CI 0.10 to 0.74). The number of potential errors about transfusion decision was 38 (13% of patients). The peripheral oxygen saturation and the true value of hemoglobin concentration were independently associated with the bias., Conclusion: Results from this widely available noninvasive point-of-care hemoglobin monitoring device were systematically biased and too unreliable to guide transfusion decisions., (Copyright © 2011 American College of Emergency Physicians. Published by Mosby, Inc. All rights reserved.)

Background: Nerve stimulation is an effective technique for peripheral nerve blockade. However, the local anesthetic (LA) distribution pattern obtained with this blind approach is unknown and may explain its clinical effects., Methods: One hundred patients received a median nerve block at the elbow using a nerve stimulator approach. After correct needle placement defined by a minimal stimulating current < or = 0.5 mA (2 Hz, 0.1 millisecond), 6 mL lidocaine 1.5%with epinephrine 1:200,000 was injected. A linear 5- to 13-MHz probe (12L-RS) was used to assess a cross-section area of median nerve, which was calculated by 3 consecutive measurements before and after injection, and LA circumferential spread around the nerve during static and longitudinal examination. Intraneural injection defined as an increase in nerve area was detected using an iterative method for outlier detection. Results of sensory tests (cold and light touch) on 3 nerve territories and of motor blockade were compared with the imaging aspects. We performed clinical neurological examination at 3 days and 1 month after block., Results: Nerve swelling, considered significant when an increase in cross-sectional area was > or = 75%, was observed in 43 patients. Nerve swelling associated with a circumferential LA spread image, present in 37 patients, was associated with a sensory success rate of 86%. The success rate was 34% for 32 patients in whom none of these signs was visualized. A circumferential spread around a nonswollen nerve, present in 25 patients, was followed by a sensory success rate of 76% within the 30-minute evaluation period. No major early neurological complications were observed., Conclusions: Nerve stimulation does not prevent intraneural injection. In the absence of intraneural injection, the presence of circumferential LA spread image seemed predictive of successful sensory block in almost 75% of the cases within the 30-minute evaluation period.

Objective: The safety, tolerability, pharmacokinetics and preliminary pharmacodynamics of single rising doses of a novel GLP-1 analog, CJC-1131, was evaluated., Methods: CJC-1131 was subcutaneously injected in 8 groups (1.5 - 20.5 microg/kg) of healthy subjects (each group of six subjects included 1 placebo per dose level). CJC-1131 was also injected subcutaneously in 6 groups (1.5 - 12 microg/kg) of Type 2 diabetic patients after a 9-day washout period from their own anti-diabetic medication. Each group of 8 patients included 2 placebo-treated patients. Seven blood glucose measurements were taken daily, and meal tolerance tests were performed on the day before dosing and on Day 3., Results: CJC-1131 was quickly absorbed from the subcutaneous space, and a less than dose-proportional increase was found in Cmax. The half-life of CJC-1131 varied from 8.9 - 14.7 days in healthy subjects and from 9.1 - 13.8 days in patients. The maximum tolerated dose in healthy subjects was established at 12 microg/kg with nausea and vomiting being the dose-limiting events. These events occurred generally in the morning after dosing. Blood glucose levels in patients decreased on Day 1 in proportion with dose, with a maximum average decrease of 4.1 mmol/l in the highest dose group. Higher doses appeared to be related to a slight weight loss in patients., Conclusions: Conjugation to albumin led to a major prolongation of the half-life of GLP-1. The tolerability of this potential antidiabetic drug seems to be limited only by gastrointestinal complaints.

Lofepramine is a tricyclic antidepressant related to imipramine. Meta-analyses were carried out with respect to efficacy and tolerability by combining outcome and adverse reaction from over 20 controlled trials comparing lofepramine with other tricyclic antidepressants. Lofepramine was at least as effective as the comparators with fewer adverse effects. In particular, the risk/benefit ratio seemed superior to the comparators amitriptyline, imipramine, clomipramine, maprotiline and desipramine.

1. In a multicenter, placebo-controlled, double-blind clinical trial in 155 elderly patients with cognitive decline, glycosaminoglycan polysulfate was found to be a therapeutically effective agent in the treatment of old age dementias. 2. Treatment with glycosaminoglycan polysulfate in the daily dosage of 600 LRU, administered on the basis of a divided dosage schedule for 12 weeks, was significantly superior to an inactive placebo on several outcome measures including the Wechsler Memory Scale-Russell Revision (Easy Paired Associates Learning and Immediate Visual Reproduction), Mini Mental State Examination, the Sandoz Clinical Assessment Geriatric (Cognitive Dysfunction and Depression), Hachinski Dementia Scale, Brief Psychiatric Rating Scale (Confusion and Depressive Withdrawal) and Global Improvement Scale of the Clinical Global Impression. 3. Adverse effects with glycosaminoglycan polysulfate were few and mild. The drug was equally well tolerated and equally effective in the two major dementias of old age, i.e., primary degenerative and multi-infarct. The number of abnormal laboratory test readings remained essentially unchanged from pre-treatment to post-treatment.

1. Dose-equivalence studies of zopiclone and triazolam were carried out. 2. Zopiclone (6.25, 8.75 and 11.25 mg), triazolam (0.1875, 0.375 and 0.5 mg) and placebo were given in the morning to 14 healthy male volunteers aged 20-25 years under double-blind conditions according to an incomplete block design. Each patient received three of the seven possible treatments at intervals of at least 1 week. Subjects were evaluated using physiological measures, rating scales and memory tasks before and 1.5 and 4.5 h after drug administration. 3. The sedative and amnestic effects of zopiclone were qualitatively similar to those of triazolam, with the highest dose of each having the greatest effect. 4. On the basis of the digit symbol substitution test, 10 mg of zopiclone is equivalent to 0.5 mg of triazolam. Methodological problems of the experimental design of dose-equivalence studies are discussed.

The use of placebos is often justified in therapeutic drug testing. They may be employed in order to compare their effects with those of a so-called active treatment, to compare two active medications, in double-blind comparisons of two drugs of different appearance (double-dummy technique) or to carry through initial washout periods. Although the scientific justification for this procedure is hardly contestable, the methodological difficulties and demands must be considered. The clinical use of placebo comparison poses a true ethical dilemma which increases with the effectiveness of psychotropic drugs. Placebos were used relatively rarely in France before 1978 as a general review of 120 controlled psychotropic drug trials published in French shows. Various precautions undertaken in drug testing designs respond, nevertheless, to both ethical and methodological demands in the majority of the cases. Examples are given regarding the testing of major or minor tranquilizers and antidepressive drugs.