A multicentred study to validate a consensus bleeding assessment tool developed by the biomedical excellence for safer transfusion collaborative for use in patients with haematological malignancy.

BACKGROUND: There continues to be uncertainty about the optimal approach to documenting bleeding data in platelet transfusion trials, with a desire to apply a common assessment tool across all trials. With this in mind, a consensus bleeding assessment tool (BAT) has been developed by the Biomedical Excellence for Safer Transfusion (BEST) collaborative, based on review of data collection forms used in published randomized trials and following content validation with a range of healthcare professionals at seven haematology centres through BEST members. This study aimed to evaluate reliability and reproducibility of the consensus BAT. METHODS: Replicated clinical assessments of bleeding were undertaken by participants with haematological malignancies recruited at four haematology centres in an international, multicentred, observational study. Concordance of repeat assessments was calculated for agreement in site and grade of bleeding observed. RESULTS: Forty patients consented to participate, and 13 trained bleeding assessors collected these data. Bleeding assessments were carried out on 113 separate days. Of all 225 bleeding assessments, 204 were compared for grade concordance, and 160 were compared for site concordance. There was very good grade concordance (83%, 95% confidence interval 74-93%) and good bleeding site concordance (69%, 95% confidence interval 57-79%) in observations of bleeding. Discordance was primarily in relation to assessing skin bleeding. CONCLUSIONS: Alongside a structured training programme, levels of concordance for a consensus BAT were high. Researchers using assessment tools for bleeding need to balance comprehensive data collection against potential loss of accuracy for some types of bleeding, such as skin findings.

A cluster-randomized trial to reduce major perinatal morbidity among women with one prior cesarean delivery in Québec (PRISMA trial): study protocol for a randomized controlled trial.

BACKGROUND: Rates of cesarean delivery are continuously increasing in industrialized countries, with repeated cesarean accounting for about a third of all cesareans. Women who have undergone a first cesarean are facing a difficult choice for their next pregnancy, i.e.: (1) to plan for a second cesarean delivery, associated with higher risk of maternal complications than vaginal delivery; or (b) to have a trial of labor (TOL) with the aim to achieve a vaginal birth after cesarean (VBAC) and to accept a significant, but rare, risk of uterine rupture and its related maternal and neonatal complications. The objective of this trial is to assess whether a multifaceted intervention would reduce the rate of major perinatal morbidity among women with one prior cesarean. METHODS/DESIGN: The study is a stratified, non-blinded, cluster-randomized, parallel-group trial of a multifaceted intervention. Hospitals in Quebec are the units of randomization and women are the units of analysis. As depicted in Figure 1, the study includes a 1-year pre-intervention period (baseline), a 5-month implementation period, and a 2-year intervention period. At the end of the baseline period, 20 hospitals will be allocated to the intervention group and 20 to the control group, using a randomization stratified by level of care. Medical records will be used to collect data before and during the intervention period. Primary outcome is the rate of a composite of major perinatal morbidities measured during the intervention period. Secondary outcomes include major and minor maternal morbidity; minor perinatal morbidity; and TOL and VBAC rate. The effect of the intervention will be assessed using the multivariable generalized-estimating-equations extension of logistic regression. The evaluation will include subgroup analyses for preterm and term birth, and a cost-effectiveness analysis. DISCUSSION: The intervention is designed to facilitate: (1) women's decision-making process, using a decision analysis tool (DAT), (2) an estimate of uterine rupture risk during TOL using ultrasound evaluation of low-uterine segment thickness, (3) an estimate of chance of TOL success, using a validated prediction tool, and (4) the implementation of best practices for intrapartum management. TRIAL REGISTRATION: Current Controlled Trials, ID: ISRCTN15346559 . Registered on 20 August 2015.

Incremental role of male circumcision on a generalised HIV epidemic through its protective effect against other sexually transmitted infections: from efficacy to effectiveness to population-level impact.

BACKGROUND: Male circumcision (MC) can reduce HIV acquisition. However, a better understanding of the indirect protective effect of MC on sexually transmitted infections (STIs) is required. OBJECTIVE: To assess the incremental benefits conferred by MC on HIV infection at the individual level in circumcision trials (no herd immunity effect) and at the population level (with herd immunity effect) owing to its protective effect against other STIs. METHODS: A dynamic stochastic model of HIV and STI infections in a Kenyan population was used to simulate the impact of MC offered to a few trial participants or to a large proportion of men in order to study the protective role of MC on HIV infection at the individual and population levels. RESULTS: Fewer than 20% of the HIV infections prevented in the circumcised arm of the circumcision trials (individual level) could be attributable to the efficacy of MC against STIs rather than against HIV. At the population level, MC can significantly reduce the prevalence of HIV, especially among men and women in the longer term. However, even at the population level, the long-term incremental impact of MC on HIV due to the protection against STI is modest (even if MC efficacy against the STI and STI prevalence was high). CONCLUSIONS: The protection of MC against STI contributes little to the overall effect of MC on HIV. Additional work is needed to determine whether, and under what conditions, the protective effect of MC efficacy against STIs can have a significant incremental benefit on the HIV epidemic.

HIV and ethnicity in Canada: is the HIV risk-taking behaviour of young foreign-born MSM similar to Canadian born MSM?

There is a dearth of information on the HIV risk-taking behaviour of foreign-born men who have sex with men (MSM) in Canada. This study focused on identifying sexual risk behaviour among MSM who immigrated to Canada and compared them to MSM who were born in Canada. Baseline data from the Omega Cohort in Montreal and the Vanguard Project in Vancouver were combined to form four ethnicity/race analytical categories (n = 1,148): White born in Canada (WBIC), White born outside of Canada, non-White born in Canada (NBIC) and non-White born outside of Canada (NBOC). Psychological, demographic and sexual behaviour characteristics of the groups were similar except: NBOC were more likely to be unemployed, less likely to be tattooed, had fewer bisexual experiences and less likely worried of insufficient funds. WBOC were more likely to report unprotected sex with seropositives and more likely to have had unprotected sex while travelling. NBIC were more likely to have ever sold sex and to have had body piercing. WBOC are at high risk of acquiring as well as transmitting HIV. It is important to consider place of birth in addition to ethnicity when developing programmes to prevent the transmission of HIV.

The effects of flaxseed dietary supplement on lipid profile, bone mineral density, and symptoms in menopausal women: a randomized, double-blind, wheat germ placebo-controlled clinical trial.

Phytoestrogens are increasingly incorporated into the diet of menopausal women. However, there are limited data on the efficacy of flaxseed on the consequences of estrogen deficiency in menopausal women. The purpose of the study was to assess the effects of flaxseed incorporation into the diet of healthy menopausal women. One hundred and ninety-nine menopausal women were randomly assigned to consume 40 g flaxseed/d (n = 101) or wheat germ placebo (n = 98) for 12 months. At baseline and at month 12, serum levels of lipids, bone mineral density (BMD), and menopausal symptoms were evaluated. Statistical analysis was performed under the intention to treat principle. Flaxseed reduced serum total (-0.20 +/- 0.51 mmol/liter; P = 0.012) and high-density lipoprotein (-0.08 +/- 0.24 mmol/liter; P = 0.031) cholesterol concentrations compared with wheat germ placebo. BMD did not differ significantly between the two arms. Both flaxseed and wheat germ reduced (P < 0.0001) the severity scores of menopausal symptoms, but no statistical difference was found between the two arms. Our findings suggest that 1-yr incorporation of flaxseed into the diet produced a favorable, but not clinically significant, effect on blood cholesterol and caused no significant change in BMD or symptoms in healthy menopausal women.

Effects of electric and magnetic fields from high-power lines on female urinary excretion of 6-sulfatoxymelatonin.

In 1998, the authors studied the effect of residential exposure to electric and magnetic fields from high-power lines on female urinary excretion of 6-sulfatoxymelatonin (6-OHMS) in the Quebec city, Canada, metropolitan area. A sample of 221 women living near a 735-kV line was compared with 195 women the same age living away from any power lines. Participants provided morning urine samples on 2 consecutive days and wore a magnetic dosimeter for 36 consecutive hours to measure personal magnetic exposure. The indoor electric field was assessed by spot measurements. After adjustment for other factors associated with low melatonin secretion, such as medication use or light exposure, nighttime concentration of 6-OHMS was similar in the two groups. When either 24-hour or sleep-time exposure to magnetic field or electric field measurements was used, no exposure-effect relation was evident. However, the trend of decreasing 6-OHMS concentration with age was more pronounced for women living near the lines, as was a lower 6-OHMS concentration in women with high body mass index. Chronic residential exposure to magnetic fields from high-power lines may accentuate the decrease in melatonin secretion observed in some vulnerable subgroups of the population.

Risk factors associated with HIV infection among young gay and bisexual men in Canada.

OBJECTIVE: To assess risk factors associated with HIV prevalence and incidence among gay and bisexual men in two prospective Canadian cohorts. METHODS: The Vanguard Project and the Omega Cohort are prospective cohort studies of gay and bisexual men ongoing in Vancouver and Montreal, respectively. For this analysis, baseline sociodemographic characteristics, sexual behavior, and substance use data from these two cohorts were combined. Assessment of risk factors for HIV seroprevalence and seroconversion were carried out using univariate and multivariate analysis. RESULTS: This analysis was based on 1373 gay and bisexual men aged 16 to 30 years. Men who were HIV-seropositive at baseline (n = 48) were more likely to report living in unstable housing, to have had less than a high school education, and to have been unemployed than those who were HIV-negative (n = 1325). HIV-positive men were also more likely to report having engaged in sexual risk behavior, including having had consensual sex at a younger age, having had at least 6 partners during the previous year, ever having been involved in the sex trade, and having engaged in unprotected receptive anal intercourse. With respect to substance use, HIV-positive men were more likely to report the use of crack, cocaine, heroin, and marijuana and to use injection drugs. Similarly, men who seroconverted during the course of the studies (n = 26) were more likely to report having less than a high school education and having lived in unstable housing at baseline. Compared with HIV-negative men, men who seroconverted were more likely to report ever having been involved in the sex trade and engaging in unprotected receptive anal intercourse. Reports of cocaine use and injection drug use were also significantly higher for men who seroconverted compared with HIV-negative men. CONCLUSIONS: Our data indicate that HIV-positive gay and bisexual men are more likely to be living in unstable conditions and to report more risky sexual and substance use behaviors than HIV-negative men.

Long-term pollution simulation in combined sewer networks.

This paper presents results of long term pollution simulations on the example of the sewerage system of Grand-Couronne. This modelling work is part of a study where objective is to develop a method to define the reference flow of a WWTP. The model HYDROWORKS DM has been successfully validated in hydraulics and pollution for the sewer network, for long time simulations. A conceptual model has been built to model the pollution in the tank at the outlet of the combined system. One synthetic year of rain has been used to simulate the working of the "up stream system" of the WWTP (combined sewer + tank + separate sewer + pre-treatments) and has been successfully validated by measurements of the 1998-1999 year. If this paper is focused on the "up stream system", the SIMBA/SIMBAD WWTP model has been successfully calibrated and validated too, and the combination represents a fully validated "Integrated Model" for the sewerage system.

Aetiology of urethral discharge in Bangui, Central African Republic.

OBJECTIVES: To determine the aetiology of urethritis in Bangui, Central African Republic. METHODS: 410 men presenting with urethral discharge and 100 asymptomatic controls were enrolled. Urethral swabs were obtained and processed by gonococcal culture and polymerase chain reaction for the detection of Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma genitalium, Trichomonas vaginalis, and Ureaplasma urealyticum. RESULTS: In multivariate analyses, M genitalium and C trachomatis were significantly associated with urethral discharge when comparing cases of non-gonococcal urethritis (NGU) with controls. T vaginalis was also more common in cases than in controls, but this reached statistical significance only among cases in whom N gonorrhoeae was also detected. U urealyticum was not associated with urethritis. The gonococcus was found in 69% of cases of urethral discharge. M genitalium was the predominant pathogen in patients with NGU, being found in 42% (53/127) of such patients while C trachomatis was found in only 17% (22/127). T vaginalis was found in 18% (23/127) of patients with NGU, but also in 15% (43/283) of patients with gonococcal urethritis, and two thirds of patients with T vaginalis also had the gonococcus. Multiple infections were common. M genitalium caused a syndrome similar to chlamydial urethritis, with a less severe inflammation than in gonococcal infection. No behavioural or clinical characteristic could discriminate between the various aetiological agents. CONCLUSIONS: M genitalium is more prevalent than C trachomatis and is the most common cause of NGU in BANGUI: It causes a syndrome similar to chlamydial urethritis. T vaginalis is weakly associated with urethritis, and is often found along with other pathogens.

Etiology of urethral discharge in West Africa: the role of Mycoplasma genitalium and Trichomonas vaginalis.

OBJECTIVE: To determine the etiological role of pathogens other than Neisseria gonorrhoeae and Chlamydia trachomatis in urethral discharge in West African men. METHODS: Urethral swabs were obtained from 659 male patients presenting with urethral discharge in 72 primary health care facilities in seven West African countries, and in 339 controls presenting for complaints unrelated to the genitourinary tract. Polymerase chain reaction analysis was used to detect the presence of N. gonorrhoeae, C. trachomatis, Trichomonas vaginalis, Mycoplasma genitalium, and Ureaplasma urealyticum. FINDINGS: N. gonorrhoeae, T. vaginalis, C. trachomatis, and M. genitalium--but not U. urealyticum--were found more frequently in men with urethral discharge than in asymptomatic controls, being present in 61.9%, 13.8%, 13.4% and 10.0%, respectively, of cases of urethral discharge. Multiple infections were common. Among patients with gonococcal infection, T. vaginalis was as frequent a coinfection as C. trachomatis. M. genitalium, T. vaginalis, and C. trachomatis caused a similar clinical syndrome to that associated with gonococcal infection, but with a less severe urethral discharge. CONCLUSIONS: M. genitalium and T. vaginalis are important etiological agents of urethral discharge in West Africa. The frequent occurrence of multiple infections with any combination of four pathogens strongly supports the syndromic approach. The optimal use of metronidazole in flowcharts for the syndromic management of urethral discharge needs to be explored in therapeutic trials.

Effects of an educational intervention on the anxiety of women awaiting mastectomies.

The purpose of this experimental study was to assess the effects of an individualized psychocognitive educational intervention on preoperative anxiety in women awaiting mastectomies. A total of 60 women aged between 27 and 65 years were randomly distributed to two groups of 30 participants. Using the Situational Anxiety Inventory (IAS) along with repeated-measures variance analysis, it was noted that, immediately following the educational interventions (both experimental and control) there was a significant reduction (p < 0.01) of anxiety with the experimental group having an additional reduction of 4.83 (p = 0.05). The day before surgery, only the experimental educational intervention resulted in a significant reduction (p = 0.03) of anxiety, but the difference between the two educational interventions was not significant. These results appear to support Lazarus and Folkman's stress, appraisal and coping theory which states that direct action on cognitive perception can influence a feeling of threat as assessed through the level of anxiety.

Some methodological issues in the study of sexual networks: from model to data to model.

BACKGROUND: Mixing between sexual activity classes is an important determinant of sexually transmitted disease transmission. However, attempts to estimate sexual mixing patterns in the field remain limited partly because of practical and methodological difficulties. GOAL: To evaluate and identify appropriate sampling schemes to estimate the mixing pattern between sexual activity classes from large population networks with one or more components. STUDY DESIGN: The study is based on simulations of large population networks with various structural characteristics. A variety of snowball sampling schemes are applied to these networks and are evaluated by the quality of the mixing matrix estimates that they produce. RESULTS AND CONCLUSIONS: Unbiased estimation of mixing patterns (global assortativity, within-group mixing of the lowest activity classes, within-group mixing of the highest activity classes) from large population networks is possible with a snowball sampling design in which the initial sample of index cases is drawn from the general population, all partners of the index case are recruited, and only one generation of partners are traced (one cycle). Simulation techniques proved useful in addressing complex methodological issues in situations where analytic results are difficult to obtain.

Risk behaviours and HIV infection among men having sexual relations with men: baseline characteristics of participants in the Omega Cohort Study, Montreal, Quebec, Canada.

OBJECTIVE: To describe characteristics of men having sex with men (MSM) participating in the Omega Cohort, to describe HIV-positive participants at baseline interview, and to estimate HIV incidence. METHODS: The Omega Cohort is a study on the incidence and psychosocial determinants of HIV infection among MSM living in Montreal. MSM complete a questionnaire and are tested for HIV every six months. RESULTS: During the previous six months, 31% and 12% of 810 participants (mean age = 33 years) reported unprotected anal sex with regular and casual partners, respectively. Eight participants (0.98%) were HIV-infected at baseline. HIV incidence was 0.89 per 100 person-years (7/787 person-years) [95% confidence interval: 0.36-1.83]. CONCLUSION: A significant proportion of participants reported current risk behaviours. Despite this, HIV incidence is relatively low. It is important to target MSM who do not practice safe sex and to encourage those practicing safe sex to sustain these behaviours.

Association of hepatitis B virus infection with other sexually transmitted infections in homosexual men. Omega Study Group.

OBJECTIVES: This study determined the prevalence and factors associated with hepatitis B virus (HBV) infection among men who have sex with men. METHODS: At the baseline visit of an HIV study among men who have sex with men, we asked about HBV vaccination status and tested for HBV markers. RESULTS: Of 625 subjects, 48% had received at least 1 dose of HBV vaccine. Of 328 unvaccinated men, 41% had 1 or more HBV markers. HBV prevalence increased markedly with age and was associated with many sexual and drug-related behaviors. In a multivariate model, 7 variables were independently associated with HBV infection: ulcerative sexually transmitted diseases (odds ratio [OR] = 10.1; 95% confidence interval [CI] = 2.6, 54); injection drug use (OR = 5.2; 95% CI = 1.2, 26); gonorrhea or chlamydia (OR = 4.0; 95% CI = 1.9, 8.9); sexual partner with HIV/AIDS (OR = 3.6; 95% CI = 1.8, 7.1); 50 or more casual partners (OR = 3.4; 95% CI = 1.6, 7.1); received money for sex (OR = 3.0; 95% CI = 1.2, 7.8); and 20 or more regular partners (OR = 2.5; 95% CI = 1.1, 6.1). CONCLUSIONS: In Montreal, men who have sex with men are at risk for HBV infection, but a substantial proportion remain unvaccinated; new strategies are required to improve coverage. Men who have sex with men and who have a sexually transmitted infection, especially a genito-ulcerative infection, appear to be at particularly high risk for HBV infection.

Delirium in terminal cancer: a prospective study using daily screening, early diagnosis, and continuous monitoring.

A pilot prospective cohort study was conducted to determine delirium frequency and outcome in cancer patients consecutively hospitalized for terminal care (median stay: 12 days). Screening for delirium symptoms was performed daily, using the Confusion Rating Scale. Patients positive on screening had a diagnostic assessment within 24 hours using the Confusion Assessment Method. Monitoring of symptoms was continued until death. Eighteen (20%) of the 89 study patients were positive on screening at admission. Among the 71 patients free of delirium at admission, the incidence of confirmed delirium was 32. 8% (95% CI, 21.3-44.3%). Patients positive on screening received a higher mean equivalent parenteral daily dose of morphine than other patients (72 mg vs. 41 mg, p = 0.08). Significant symptom improvement occurred in 16 (50%) of the 32 delirious cases. Delirium is a serious and frequent complication in terminal cancer whose outcome may not be as poor as previously considered.

Correlates of risky behaviors among young and older men having sexual relations with men in Montréal, Québec, Canada. Omega Study Group.

OBJECTIVE: To assess characteristics associated with 1) age and 2) recent unprotected anal sex with casual partners among men having sexual relations with men (MSM) participating in the Omega Cohort, Montréal, Québec, Canada. METHODS: The Omega Cohort is a study of the incidence and psychosocial determinants of HIV infection among MSM living in Montréal. MSM complete a questionnaire and are tested for HIV every 6 months. RESULTS: Thirteen percent of young MSM (< 30 years of age, n = 355) and 12% of older MSM (> or = 30 years of age, n = 455) reported recent unprotected anal sex with casual partners. The predictors of this latter behavior were: not living with a male sexual partner, unprotected anal sex with regular partner, > 5 casual partners, alcohol/drug use before anal sex, and having difficulties with procedures needed for safe sex. Among young MSM, additional predictors were: to have been living in Montreal for less than 1 year and to have exchanged money for sex. Among older MSM, additional predictors were: female sexual partners, unprotected anal sex with an HIV-infected partner, and feeling invulnerable to AIDS. CONCLUSION: Young Omega participants do not have more risky behaviors than older participants. Some predictors of recent risk behaviors with casual partners were different between the two groups. Prevention programs should be adapted consequently.

Simulation studies of phase III clinical trials to test the efficacy of a candidate HIV-1 vaccine.

One question of particular importance in phase III HIV vaccine trials is the choice of efficacy measure (EM) to validly and precisely estimate the true vaccinal efficacy. Traditional EMs, based on hazard rate ratio (HRR) or cumulative incidence ratio (CIR) are time-sensitive to mode of vaccine action and population heterogeneities. Through Monte-Carlo simulation, the performance of HRR and CIR based EMs are examined across different trial designs and vaccine and population characteristics. A new EM based on log-spline hazard regression (HARE) is proposed. Given that vaccinal properties (mode of action, time-lag, waning) are unknown a priori, appropriate selection of EM is problematic, and HRR and CIR can be unreliable to estimate the true maximum efficacy of candidate products. Non-random sexual mixing can exacerbate biases in HRR and CIR. HARE can offer valid estimation across different modes of vaccine action and in presence of frailty effects, contrary to its traditional counterparts. Our simulation studies highlight the weaknesses of widely used EMs while offering guidelines for trial design and suggesting new avenues for statistical analysis.

Massive activation-induced cell death of alloreactive T cells with apoptosis of bystander postthymic T cells prevents immune reconstitution in mice with graft-versus-host disease.

After hematopoietic stem cell transplantation, the persistence and expansion of grafted mature postthymic T cells allow both transfer of donor immunologic memory and generation of a diverse T repertoire. This thymic-independent process, which is particularly important in humans, because most transplant recipients present severe thymus atrophy, is impaired by graft-versus-host disease (GVHD). The goal of this study was to decipher how GVHD influences the fate of grafted postthymic T cells. Two major findings emerged. First, we found that, after a brisk proliferation phase, alloreactive antihost T cells underwent a massive activation-induced cell death (AICD). For both CD4(+) and CD8(+) T cells, the Fas pathway was found to play a major role in this AICD: alloreactive T cells upregulated Fas and FasL, and AICD of antihost T cells was much decreased in the case of lpr (Fas-deficient) donors. Second, whereas non-host-reactive donor T cells neither upregulated Fas nor suffered apoptosis when transplanted alone, they showed increased membrane Fas expression and apoptosis when coinjected with host-reactive T cells. We conclude that GVHD-associated AICD of antihost T cells coupled with bystander lysis of grafted non-host-reactive T cells abrogate immune reconstitution by donor-derived postthymic T lymphocytes. Furthermore, we speculate that massive lymphoid apoptosis observed in the acute phase of GVHD might be responsible for the occurrence of autoimmunity in the chronic phase of GVHD.

Factors associated with hepatitis B vaccination among men having sexual relations with men in Montreal, Quebec, Canada. Omega Study Group.

OBJECTIVE: To determine factors associated with hepatitis B virus (HBV) vaccination status among HIV-uninfected men who have affective and sexual relations with men (MASM) in Montreal, Quebec, Canada. METHODS: The Omega Cohort is a study of the incidence and psychosocial determinants of HIV infection among MASM in Montreal. Participants complete a questionnaire and are HIV-tested every 6 months. At baseline, we also performed testing for HBV markers and collected data on HBV vaccination history. RESULTS: Forty-six percent of 653 participants had received at least one dose of HBV vaccination, whereas 28% were completely vaccinated. Lack of vaccination was associated with injection drug use, having > or =20 regular lifetime partners, living outside Montreal, not having sex in bathhouses, and not having consulted a physician aware of the participant's sexual orientation. Among vaccinated MASM, incomplete vaccination was associated with having <20 lifetime casual partners, trading sex for drugs, having given goods for sex, having had unprotected anal sex with regular partners, and having no history of a previous sexually transmitted disease. CONCLUSION: A significant proportion of Montreal's MASM, some of whom are at risk of contracting HBV through sexual and parenteral transmission, have not been vaccinated for HBV. Men who have affective and sexual relations with men should be educated about the risk of HBV transmission and the seriousness of the disease.