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.

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.

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.

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.

Long-term quality of life after breast cancer: comparison of 8-year survivors with population controls.

PURPOSE: Quality of life of breast cancer survivors 8 years after diagnosis was compared with that among similarly aged women who had never confronted cancer (controls). METHODS: Survivors of a consecutive series of 227 breast cancer patients first treated in 1984 were approached for this study. Random-digit dialing was used to identify controls with the same age and residential distribution as the survivors. Quality of life was assessed in terms of physical health, functional status, psychologic distress, and social functioning. RESULTS: Participation was obtained from 96% (n = 124) of 129 eligible survivors and 61% (n = 262) of 427 potentially eligible controls. Consistently smaller proportions of survivors reported positive quality-of-life outcomes compared with controls, but these differences were generally small and nonsignificant statistically. When limited to women who remained free of disease over the entire follow-up period (n = 98), survivors' quality of life was similar to that among controls, with the exception of arm problems and sexual satisfaction for those women who lived with a partner. In contrast, survivors who developed recurrence or new primary breast cancer (n = 26) experienced a worse quality of life in all domains except social functioning. CONCLUSION: In most domains and for women without further disease events after diagnosis, quality of life does not seem to be permanently and globally impaired by breast cancer. Consequently, breast cancer survivors who remain free of disease probably do not need organized late psychosocial follow-up to improve quality of life. However, arm problems and sexuality are two areas in which additional effort may be still needed to improve quality of life of long-term survivors.

Inhibitors of permeability transition interfere with the disruption of the mitochondrial transmembrane potential during apoptosis.

In a number of experimental systems, the early stage of the apoptotic process, i.e. the stage which precedes nuclear disintegration, is characterized by the breakdown of the inner mitochondrial transmembrane potential (delta psi m). Here we address the question as to whether mitochondrial permeability transition (PT) pores may account for the delta psi m dissipation in lymphocyte apoptosis. Drugs known for their PT-inhibitory potential (bongkrekic acid, cyclosporin A, and the non-immunosuppressive cyclosporin A analogue N-methyl-Val-4-cyclosporin A) are capable of preventing the apoptotic delta psi m disruption. Moreover, pharmacological modulation of PT-mediated delta psi m dissipation can prevent apoptosis. Thus, while suppressing the delta psi m disruption, bongkrekic acid also inhibits the apoptotic chromatinolysis. In conclusion, these data are compatible with the hypothesis that apoptotic delta psi m disruption is mediated by the formation of PT pores and that PT-mediated delta psi m disruption is a critical event of the apoptotic cascade.

Early disruptive behavior, poor school achievement, delinquent behavior, and delinquent personality: longitudinal analyses.

Three alternative models concerning the causal links between early disruptive behavior, poor school achievement, and delinquent behavior or antisocial personality were tested with linear structural equation modeling. Subjects were boys and girls followed from first grade to age 14. Disruptive behavior was assessed in Grade 1; school achievement was assessed in Grades 1 and 4; delinquent behavior and antisocial personality were assessed at age 14. With regard to self-reported delinquent behavior at age 14, results indicate that the best model for boys was a direct causal link between Grade 1 disruptive behavior and delinquent behavior. Poor school achievement was not a necessary causal factor. For girls, none of the tested models were a good fit to the delinquent behavior data. As for delinquent personality, results indicate that, for both boys and girls, poor school achievement was a necessary component of the causal path between Grade 1 disruptive behavior and age 14 delinquent personality.

Oral torsemide in patients with chronic congestive heart failure: effects on body weight, edema, and electrolyte excretion. Torsemide Investigators Group.

STUDY OBJECTIVE: To assess the effects of torsemide on the primary end point of change in body weight from baseline, and the following secondary end points: urinary sodium, potassium, and chloride excretion, and urine volume after the first dose of drug. DESIGN: Randomized, parallel, double-blind, multicenter study in patients treated with torsemide 5 mg (n = 19), 10 mg (n = 18), or 20 mg (n = 14), or placebo (n = 15) for 7 days. PATIENTS: Sixty-six patients with New York Heart Association class II or III congestive heart failure and edema. RESULTS: At the end of the study, patients treated with torsemide 10 and 20 mg demonstrated a significant reduction in body weight compared with those receiving placebo (-1.62 and -1.30 kg, respectively), and those treated with torsemide 5 mg did not (-0.60 kg). The severity of edema decreased with increasing torsemide dose. Torsemide caused no greater frequency of adverse effects with increasing dose. CONCLUSION: Orally administered torsemide 5, 10, and 20 mg once/day for 7 days were well tolerated. Doses of 10 and 20 mg were effective in producing weight loss.

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.

Comparison of body mass indexes and cutoff points for estimating the prevalence of overweight in Hispanic women.

The anthropometric standards used for estimating the prevalence of overweight among Hispanic groups are generally developed in other populations. Our purpose was to identify appropriate anthropometric indicators and cutoff points for Hispanic women. Data from the Hispanic Health and Nutrition Examination Survey HHANES (1982-1984) included 1,784 Mexican American, 479 Cuban American, and 750 Puerto Rico women aged 25 to 74 years. The body mass indexes examined were weight/standing height1.5, weight/standing height2, weight/sitting height1.5, and weight/sitting height2. Appropriateness was based on correlation of the index with triceps and subscapular skinfold measurements and lack of association with standing or sitting height. The most appropriate indicator was weight/standing height2. To estimate overweight, the 85th percentiles for weight/standing height2 were obtained from the 20- to 29-year-olds in HHANES and the second National Health and Nutrition Examination Survey (NHANES II). For 10-year age intervals, the differences in proportions of women above those cutoff points were compared with a modified t test. The mean estimated prevalences of overweight were significantly higher with the NHANES II standard compared with the HHANES cutoff points (P < .05) for Mexican American women (43% vs 29%) and Puerto Rican women (40% vs 28%). They were slightly lower for the Cuban American women (36% vs 39%). Cutoff points are relative, not absolute, standards that must have biologic meaning. Before our results are used for assessing populations, the cutoff points should be tested for predictive validity with chronic disease rates.

Gender-, side- and site-dependent variations in human perioral spatial resolution.

Twenty-eight right-handed, young adults participated in a sensory testing experiment to evaluate spatial resolution at 10 positionally matched sites on the right- and left-hand sides of the face. An adaptive psychophysical (i.e. tracking) procedure was used to estimate the threshold spatial separation for perceiving two points of contact at each site. Estimates of the threshold at one site on both sides of the face were also obtained with a method-of-limits procedure similar to that employed for clinical evaluation of patients. In addition, each individual was asked to rate (i) his(her) overall facial sensitivity to touch and (ii) the degree to which he(she) could discern subtle changes in lip, cheek and chin position during speech, chewing and facial expression. Analysis of the estimates of the threshold separation obtained with the tracking procedure revealed a significant effect of gender (p < 0.04) and of site (p < 0.001). Females were more spatially sensitive than males: average threshold separations were 1.55 mm less. Most notably, the threshold increased ninefold with distance posterolaterally from the oral opening. The vermilion of the upper lip was the most spatially sensitive site (population geometric mean = 2.4 mm) and the preauricular skin the least spatially sensitive site (20.9 mm). Significant effects of side and of interactions among gender, side and site were not observed. The estimates obtained with the method-of-limits procedure were very similar to those obtained with the tracking procedure: the latter were 0.67 mm less on the average. Individuals' ratings of overall facial sensitivity to touch were similar for males and females (p > 0.70). Females, however, reported greater ability to discern subtle changes in lip, cheek and chin position than males (p < 0.03). The ratings of this sensory function correlated negatively with the estimates of the threshold separation on the vermilion of the upper lip (p < 0.03).

Job strain and ambulatory blood pressure among female white-collar workers.

OBJECTIVES: The association between job strain and ambulatory blood pressure was studied among female white-collar workers. METHODS: This cross-sectional investigation studied 210 women in high- or low-strain jobs randomly selected from 3183 women of all ages, employed as white-collar workers. The women wore an ambulatory blood pressure monitor for 24 hours during a workday. Mean blood pressures were calculated. Psychological demands and decisional latitude were measured twice (14 months before and 7 days before the blood pressure measurement) with 2 scales recommended by Karasek. RESULTS: Significant differences in blood pressure were found according to current job strain among the women holding a university degree. Their mean blood pressures during work were significantly higher [8.0 mm Hg (1.1 kPa) systolic and 6.4 mm Hg (0.8 kPa) diastolic blood pressure] in the high-strain group than in the low-strain group. Statistically significant elevations in blood pressure over the 24-hour period were also found for women with a university degree. Cumulative exposure to high strain over 14 months was also significantly associated with high systolic blood pressure at work, in the evening, and over a 24-hour period irrespective of other factors related to blood pressure. Among the women without a university degree, the blood pressure differences observed between the job strain groups were less than 1 mm Hg (0.1 kPa) and not statistically significant. CONCLUSIONS: These results provide support for the effect of job strain on ambulatory blood pressure only among female white-collar workers holding a university degree.

Mathematical models of disease transmission: a precious tool for the study of sexually transmitted diseases.

This paper is an introduction to the mathematical epidemiology of sexually transmitted diseases (STDs) and its application to public health. After a brief introduction to transmission dynamics models, the construction of a deterministic compartmental mathematical model of HIV transmission in a population is described. As a background to STD transmission dynamics, basic reproductive rate, intergroup mixing, rate of partner change, and duration of infectivity are discussed. Use of the models illustrates the effect of sexual mixing (proportionate to highly assortative), of preventive intervention campaigns, and of HIV-chlamydia interaction on HIV prevalence in the different population groups. In particular, planned prevention campaigns can benefit the targeted intervention group but surprisingly can be disadvantageous for the general population. Through examples, mathematical models are shown to be helpful in our understanding of disease transmission, in interpretation of observed trends, in planning of prevention strategies, and in guiding data collection.

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.

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.

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.

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.

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.

Passive immunity against measles during the first 8 months of life of infants born to vaccinated mothers or to mothers who sustained measles.

Neutralizing antibody titers of 47 infants whose mothers sustained measles (measles group) and 70 whose mothers were vaccinated (vaccine group) were compared at birth, 4 and 8 months of age. All children had antibodies at birth and 88% at 4 months. At 8 months, 49% had antibodies in the measles group and 15% in the vaccine group (P < 0.001). The geometric mean titers were significantly lower in the vaccine group than in the measles group and the difference corresponded to the antibody loss occurring in only 1.5 months of life. This small difference may reflect past exposure to wild virus of many vaccinated mothers.

Highlights of the sexual activity of the heterosexual population in the province of Quebec.

OBJECTIVES: To describe and quantify the level of sexual activity of the heterosexually active population of Quebec. METHODS: The data analysed included 2889 heterosexually active individuals aged 15-60 (agemed = 32) from a 1996-7 survey on the sexual lifestyles of the general population of Quebec. Various probability distributions were studied to assess their capacity to describe and quantify the lifetime and yearly numbers of sexual partners of the sampled population. To estimate the annual rates of new partner acquisition, a generalised linear model was fitted to the number of lifetime sexual partners as a function of age, years of sexual activity, and sex. RESULTS: The mean and variance of the number of lifetime sexual partners for men (mean = 11, s2 = 163) is higher than for women (mean = 6, s2 = 72). The negative binomial and lognormal probability distributions give the most adequate fit to the lifetime number of partners for both agglomerated and stratified (by sex and age) data. The estimated annual rates of new partner acquisition provide two important results for prevention: (1) the first year of sexual activity represents the highest annual rate of new partner acquisition independent of age, (2) annual rates of new partner acquisitions increase through mid-life (ages 40-50) combined with a decrease in condom use. CONCLUSION: Problems caused by the use of large categories in the estimation of mean and variance cannot totally be overcome by fitting probability distributions to the empirical data despite good fits. Furthermore, we believe that adequate estimates of the annual rate of new partner acquisition should be a better measure of the risk of HIV infection than the number of partners since the first is a measure of incidence while the second is a measure of prevalence.