International differences in alcohol use according to sexual orientation.

Most research on sexual orientation and alcohol use in the United States has found higher rates of alcohol use and abuse among gay men and lesbians. Studies from other countries have found smaller or no differences between sexual minority and heterosexual women and men. The present study used general population survey data from 14 countries to examine high-volume and risky single-occasion drinking by sexual orientation. Data from 248 gay men and lesbians and 3720 heterosexuals were analyzed in a case-control design. In several countries partnered or recently partnered gay men and lesbians had no greater risk of heavy drinking or engaging in heavy drinking than heterosexual controls. Only lesbians in North America showed higher risk for both indicators. Future general population health research should include larger samples of gays and lesbians and use more comprehensive measures of sexual orientation for investigating the prevalence of health risk factors.

Randomized Trial of prophylactic granulocyte colony-stimulating factor during rapid COJEC induction in pediatric patients with high-risk neuroblastoma: the European HR-NBL1/SIOPEN study.

Purpose To reduce the incidence of febrile neutropenia during rapid COJEC (cisplatin, vincristine, carboplatin, etoposide, and cyclophosphamide given in a rapid delivery schedule) induction. In the High-Risk Neuroblastoma-1 (HR-NBL1) trial, the International Society of Paediatric Oncology European Neuroblastoma Group (SIOPEN) randomly assigned patients to primary prophylactic (PP) versus symptom-triggered granulocyte colony-stimulating factor (GCSF; filgrastim). Patients and Methods From May 2002 to November 2005, 239 patients in 16 countries were randomly assigned to receive or not receive PPGCSF. There were 144 boys with a median age of 3.1 years (range, 1 to 17 years) of whom 217 had International Neuroblastoma Staging System (INSS) stage 4 and 22 had stage 2 or 3 MYCN-amplified disease. The prophylactic arm received a single daily dose of 5 μg/kg GCSF, starting after each of the eight COJEC chemotherapy cycles and stopping 24 hours before the next cycle. Chemotherapy was administered every 10 days regardless of hematologic recovery, provided that infection was controlled. Results The PPGCSF arm had significantly fewer febrile neutropenic episodes (P = .002), days with fever (P = .004), hospital days (P = .017), and antibiotic days (P = .001). Reported Common Toxicity Criteria (CTC) graded toxicity was also significantly reduced: infections per cycle (P = .002), fever (P < .001), severe leucopenia (P < .001), neutropenia (P < .001), mucositis (P = .002), nausea/vomiting (P = .045), and constipation (P = .008). Severe weight loss was reduced significantly by 50% (P = .013). Protocol compliance with the rapid induction schedule was also significantly better in the PPGCSF arm shown by shorter time to completion (P = .005). PPGCSF did not adversely affect response rates or success of peripheral-blood stem-cell harvest. Following these results, PPG-GSF was advised for all patients on rapid COJEC induction.

Pacemaker therapy in patients with neurally mediated syncope and documented asystole: Third International Study on Syncope of Uncertain Etiology (ISSUE-3): a randomized trial.

BACKGROUND: The efficacy of cardiac pacing for prevention of syncopal recurrences in patients with neurally mediated syncope is controversial. We wanted to determine whether pacing therapy reduces syncopal recurrences in patients with severe asystolic neurally mediated syncope. METHODS AND RESULTS: Double-blind, randomized placebo-controlled study conducted in 29 centers in the Third International Study on Syncope of Uncertain Etiology (ISSUE-3) trial. Patients were ≥40 years, had experienced ≥3 syncopal episodes in the previous 2 years. Initially, 511 patients, received an implantable loop recorder; 89 of these had documentation of syncope with ≥3 s asystole or ≥6 s asystole without syncope within 12 ± 10 months and met criteria for pacemaker implantation; 77 of 89 patients were randomly assigned to dual-chamber pacing with rate drop response or to sensing only. The data were analyzed on intention-to-treat principle. There was syncope recurrence during follow-up in 27 patients, 19 of whom had been assigned to pacemaker OFF and 8 to pacemaker ON. The 2-year estimated syncope recurrence rate was 57% (95% CI, 40-74) with pacemaker OFF and 25% (95% CI, 13-45) with pacemaker ON (log rank: P=0.039 at the threshold of statistical significance of 0.04). The risk of recurrence was reduced by 57% (95% CI, 4-81). Five patients had procedural complications: lead dislodgment in 4 requiring correction and subclavian vein thrombosis in 1 patient. CONCLUSIONS: Dual-chamber permanent pacing is effective in reducing recurrence of syncope in patients ≥40 years with severe asystolic neurally mediated syncope. The observed 32% absolute and 57% relative reduction in syncope recurrence support this invasive treatment for the relatively benign neurally mediated syncope. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00359203.

Phase III study of ACVBP versus ACVBP plus rituximab for patients with localized low-risk diffuse large B-cell lymphoma (LNH03-1B).

Background The superiority of a chemotherapy with doxorubicin, cyclophosphamide, vindesine, bleomycin and prednisone (ACVBP) in comparison with cyclophosphamide, doxorubicin, vincristin and prednisone plus radiotherapy for young patients with localized diffuse large B-cell lymphoma (DLBCL) was previously demonstrated. We report the results of a trial which evaluates the role of rituximab combined with ACVBP (R-ACVBP) in these patients. Patients and methods Untreated patients younger than 66 years with stage I or II DLBCL and no adverse prognostic factors of the age-adjusted International Prognostic Index were randomly assigned to receive three cycles of ACVBP plus sequential consolidation with or without the addition of four infusions of rituximab. Results A total of 223 patients were randomly allocated to the study, 110 in the R-ACVBP group and 113 in the ACVBP group. After a median follow-up of 43 months, our 3-year estimate of event-free survival was 93% in the R-ACVBP group and 82% in the ACVBP group (P = 0.0487). Three-year estimate of progression-free survival was increased in the R-ACVBP group (95% versus 83%, P = 0.0205). Overall survival did not differ between the two groups with a 3-year estimates of 98% and 97%, respectively (P = 0.686). Conclusion In young patients with low-risk localized DLBCL, rituximab combined with three cycles of ACVBP plus consolidation is significantly superior to ACVBP plus consolidation alone.

Current features of infective endocarditis in elderly patients: results of the International Collaboration on Endocarditis Prospective Cohort Study.

BACKGROUND: Elderly patients are emerging as a population at high risk for infective endocarditis (IE). However, adequately sized prospective studies on the features of IE in elderly patients are lacking. METHODS: In this multinational, prospective, observational cohort study within the International Collaboration on Endocarditis, 2759 consecutive patients were enrolled from June 15, 2000, to December 1, 2005; 1056 patients with IE 65 years or older were compared with 1703 patients younger than 65 years. Risk factors, predisposing conditions, origin, clinical features, course, and outcome of IE were comprehensively analyzed. RESULTS: Elderly patients reported more frequently a hospitalization or an invasive procedure before IE onset. Diabetes mellitus and genitourinary and gastrointestinal cancer were the major predisposing conditions. Blood culture yield was higher among elderly patients with IE. The leading causative organism was Staphylococcus aureus, with a higher rate of methicillin resistance. Streptococcus bovis and enterococci were also significantly more prevalent. The clinical presentation of elderly patients with IE was remarkable for lower rates of embolism, immune-mediated phenomena, or septic complications. At both echocardiography and surgery, fewer vegetations and more abscesses were found, and the gain in the diagnostic yield of transesophageal echocardiography was significantly larger. Significantly fewer elderly patients underwent cardiac surgery (38.9% vs 53.5%; P < .001). Elderly patients with IE showed a higher rate of in-hospital death (24.9% vs 12.8%; P < .001), and age older than 65 years was an independent predictor of mortality. CONCLUSIONS: In this large prospective study, increasing age emerges as a major determinant of the clinical characteristics of IE. Lower rates of surgical treatment and high mortality are the most prominent features of elderly patients with IE. Efforts should be made to prevent health care-associated acquisition and improve outcomes in this major subgroup of patients with IE.

International Society of Urological Pathology (ISUP) Consensus Conference on Handling and Staging of Radical Prostatectomy Specimens. Working group 4: seminal vesicles and lymph nodes.

The 2009 International Society of Urological Pathology Consensus Conference in Boston made recommendations regarding the standardization of pathology reporting of radical prostatectomy specimens. Issues relating to the infiltration of tumor into the seminal vesicles and regional lymph nodes were coordinated by working group 4. There was a consensus that complete blocking of the seminal vesicles was not necessary, although sampling of the junction of the seminal vesicles and prostate was mandatory. There was consensus that sampling of the vas deferens margins was not obligatory. There was also consensus that muscular wall invasion of the extraprostatic seminal vesicle only should be regarded as seminal vesicle invasion. Categorization into types of seminal vesicle spread was agreed by consensus to be not necessary. For examination of lymph nodes, there was consensus that special techniques such as frozen sectioning were of use only in high-risk cases. There was no consensus on the optimal sampling method for pelvic lymph node dissection specimens, although there was consensus that all lymph nodes should be completely blocked as a minimum. There was also a consensus that a count of the number of lymph nodes harvested should be attempted. In view of recent evidence, there was consensus that the diameter of the largest lymph node metastasis should be measured. These consensus decisions will hopefully clarify the difficult areas of pathological assessment in radical prostatectomy evaluation and improve the concordance of research series to allow more accurate assessment of patient prognosis.

Combining clinical factors and quantitative ultrasound improves the detection of women both at low and high risk for hip fracture.

We hypothesized that combining clinical risk factors (CRF) with the heel stiffness index (SI) measured via quantitative ultrasound (QUS) would improve the detection of women both at low and high risk for hip fracture. Categorizing women by risk score improved the specificity of detection to 42.4%, versus 33.8% using CRF alone and 38.4% using the SI alone. This combined CRF-SI score could be used wherever and whenever DXA is not readily accessible. INTRODUCTION AND HYPOTHESIS: Several strategies have been proposed to identify women at high risk for osteoporosis-related fractures; we wanted to investigate whether combining clinical risk factors (CRF) and heel QUS parameters could provide a more accurate tool to identify women at both low and high risk for hip fracture than either CRF or QUS alone. METHODS: We pooled two Caucasian cohorts, EPIDOS and SEMOF, into a large database named "EPISEM", in which 12,064 women, 70 to 100 years old, were analyzed. Amongst all the CRF available in EPISEM, we used only the ones which were statistically significant in a Cox multivariate model. Then, we constructed a risk score, by combining the QUS-derived heel stiffness index (SI) and the following seven CRF: patient age, body mass index (BMI), fracture history, fall history, diabetes history, chair-test results, and past estrogen treatment. RESULTS: Using the composite SI-CRF score, 42% of the women who did not report a hip fracture were found to be at low risk at baseline, and 57% of those who subsequently sustained a fracture were at high risk. Using the SI alone, corresponding percentages were 38% and 52%; using CRF alone, 34% and 53%. The number of subjects in the intermediate group was reduced from 5,400 (including 112 hip fractures) and 5,032 (including 111 hip fractures) to 4,549 (including 100 including fractures) for the CRF and QUS alone versus the combination score. CONCLUSIONS: Combining clinical risk factors to heel bone ultrasound appears to correctly identify more women at low risk for hip fracture than either the stiffness index or the CRF alone; it improves the detection of women both at low and high risk.

Sharing and Learning= Changing. A real story at the Institute of Public Security of Catalonia

The Institute has professionals with extensive experience in training, specifically with experience in the field of police and emergencies training. Moreover, it also has very talented people. But above all, our institution has public professionals with a desire to serve, who love security and emergency responders and want to provide them with the best knowledge to make them every day better professionals. In the quest for continuous training improvement, its during 2009 when e-learning begins to have a presence at the Institute. Virtual training methodology becomes a facilitator for the training of various professionals, avoiding geographical displacement and easing the class schedule.

Official Positions for FRAX® clinical regarding biochemical markers from Joint Official Positions Development Conference of the International Society for Clinical Densitometry and International Osteoporosis Foundation on FRAX®.

The best indirect evidence that increased bone turnover contributes to fracture risk is the fact that most of the proven therapies for osteoporosis are inhibitors of bone turnover. The evidence base that we can use biochemical markers of bone turnover in the assessment of fracture risk is somewhat less convincing. This relates to natural variability in the markers, problems with the assays, disparity in the statistical analyses of relevant studies and the independence of their contribution to fracture risk. More research is clearly required to address these deficiencies before biochemical markers might contribute a useful independent risk factor for inclusion in FRAX(®).

Oral versus intravenous empirical antimicrobial therapy for fever in patients with granulocytopenia who are receiving cancer chemotherapy. International Antimicrobial Therapy Cooperative Group of the European Organization for Research and Treatment of Cancer.

BACKGROUND: Intravenously administered antimicrobial agents have been the standard choice for the empirical management of fever in patients with cancer and granulocytopenia. If orally administered empirical therapy is as effective as intravenous therapy, it would offer advantages such as improved quality of life and lower cost. METHODS: In a prospective, open-label, multicenter trial, we randomly assigned febrile patients with cancer who had granulocytopenia that was expected to resolve within 10 days to receive empirical therapy with either oral ciprofloxacin (750 mg twice daily) plus amoxicillin-clavulanate (625 mg three times daily) or standard daily doses of intravenous ceftriaxone plus amikacin. All patients were hospitalized until their fever resolved. The primary objective of the study was to determine whether there was equivalence between the regimens, defined as an absolute difference in the rates of success of 10 percent or less. RESULTS: Equivalence was demonstrated at the second interim analysis, and the trial was terminated after the enrollment of 353 patients. In the analysis of the 312 patients who were treated according to the protocol and who could be evaluated, treatment was successful in 86 percent of the patients in the oral-therapy group (95 percent confidence interval, 80 to 91 percent) and 84 percent of those in the intravenous-therapy group (95 percent confidence interval, 78 to 90 percent; P=0.02). The results were similar in the intention-to-treat analysis (80 percent and 77 percent, respectively; P=0.03), as were the duration of fever, the time to a change in the regimen, the reasons for such a change, the duration of therapy, and survival. The types of adverse events differed slightly between the groups but were similar in frequency. CONCLUSIONS: In low-risk patients with cancer who have fever and granulocytopenia, oral therapy with ciprofloxacin plus amoxicillin-clavulanate is as effective as intravenous therapy.

Official Positions for FRAX® clinical regarding falls and frailty: can falls and frailty be used in FRAX®? From Joint Official Positions Development Conference of the International Society for Clinical Densitometry and International Osteoporosis Foundation on FRAX®.

Risk factors for fracture can be purely skeletal, e.g., bone mass, microarchitecture or geometry, or a combination of bone and falls risk related factors such as age and functional status. The remit of this Task Force was to review the evidence and consider if falls should be incorporated into the FRAX® model or, alternatively, to provide guidance to assist clinicians in clinical decision-making for patients with a falls history. It is clear that falls are a risk factor for fracture. Fracture probability may be underestimated by FRAX® in individuals with a history of frequent falls. The substantial evidence that various interventions are effective in reducing falls risk was reviewed. Targeting falls risk reduction strategies towards frail older people at high risk for indoor falls is appropriate. This Task Force believes that further fracture reduction requires measures to reduce falls risk in addition to bone directed therapy. Clinicians should recognize that patients with frequent falls are at higher fracture risk than currently estimated by FRAX® and include this in decision-making. However, quantitative adjustment of the FRAX® estimated risk based on falls history is not currently possible. In the long term, incorporation of falls as a risk factor in the FRAX® model would be ideal.

Leverage and beliefs: Personal experience and risk taking in margin lending

What determines risk-bearing capacity and the amount of leverage in financial markets? Thispaper uses unique micro-data on collateralized lending contracts during a period of financialdistress to address this question. An investor syndicate speculating in English stocks wentbankrupt in 1772. Using hand-collected information from Dutch notarial archives, we examinechanges in lenders' behavior following exposure to potential (but not actual) losses. Before thedistress episode, financiers that lent to the ill-fated syndicate were indistinguishable from therest. Afterwards, they behaved differently: they lent with much higher haircuts. Only lendersexposed to the failed syndicate altered their behavior. The differential change is remarkable sincethe distress was public knowledge, and because none of the lenders suffered actual losses ? allfinanciers were repaid in full. Interest rates were also unaffected; the market balanced solelythrough changes in collateral requirements. Our findings are consistent with a heterogeneousbeliefs-interpretation of leverage. They also suggest that individual experience can modify thelevel of leverage in a market quickly.

A database to aid the identification of chemicals potentially posing a health risk through percutaneous exposure

In the context of recent attempts to redefine the 'skin notation' concept, a position paper summarizing an international workshop on the topic stated that the skin notation should be a hazard indicator related to the degree of toxicity and the potential for transdermal exposure of a chemical. Within the framework of developing a web-based tool integrating this concept, we constructed a database of 7101 agents for which a percutaneous permeation constant can be estimated (using molecular weight and octanol-water partition constant), and for which at least one of the following toxicity indices could be retrieved: Inhalation occupational exposure limit (n=644), Oral lethal dose 50 (LD50, n=6708), cutaneous LD50 (n=1801), Oral no observed adverse effect level (NOAEL, n=1600), and cutaneous NOAEL (n=187). Data sources included the Registry of toxic effects of chemical substances (RTECS, MDL information systems, Inc.), PHYSPROP (Syracuse Research Corp.) and safety cards from the International Programme on Chemical Safety (IPCS). A hazard index, which corresponds to the product of exposure duration and skin surface exposed that would yield an internal dose equal to a toxic reference dose was calculated. This presentation provides a descriptive summary of the database, correlations between toxicity indices, and an example of how the web tool will help industrial hygienist decide on the possibility of a dermal risk using the hazard index.