Transmission of Chlamydia trachomatis through sexual partnerships: a comparison between three individual-based models and empirical data

Chlamydia trachomatis is the most common bacterial sexually transmitted infection (STI) in many developed countries. The highest prevalence rates are found among young adults who have frequent partner change rates. Three published individual-based models have incorporated a detailed description of age-specific sexual behaviour in order to quantify the transmission of C. trachomatis in the population and to assess the impact of screening interventions. Owing to varying assumptions about sexual partnership formation and dissolution and the great uncertainty about critical parameters, such models show conflicting results about the impact of preventive interventions. Here, we perform a detailed evaluation of these models by comparing the partnership formation and dissolution dynamics with data from Natsal 2000, a population-based probability sample survey of sexual attitudes and lifestyles in Britain. The data also allow us to describe the dispersion of C. trachomatis infections as a function of sexual behaviour, using the Gini coefficient. We suggest that the Gini coefficient is a useful measure for calibrating infectious disease models that include risk structure and highlight the need to estimate this measure for other STIs.

Psychosocial stress and cardiovascular risk : current opinion

Cardiovascular disease (CVD) is a major cause of morbidity and mortality worldwide. Epidemiologic research of the last half-century has clearly shown that psychosocial factors related to the social environment, personality characteristics, and negative affect increase the risk of incident CVD and also impact prognosis of cardiac patients. Several mechanisms may explain this link, including a genetic predisposition, poor lifestyle choices, low adherence to health recommendations, and direct pathophysiologic perturbations. The latter include alteration of the hypothalamic-pituitary adrenal axis and autonomic dysfunction resulting in endothelial dysfunction, inflammation, and a prothrombotic state further downstream. Screening for psychosocial factors seems appropriate as part of the standard history and based on the clinician's knowledge of the patient and the purpose of the visit. Psychological interventions generally alleviate distress in cardiac patients, but whether they reduce the risk of hard cardiovascular endpoints and all-cause mortality is less evident. Cardiac patients with more severe depression may particularly profit from antidepressant medications. Due to their pharmacologic properties, selective serotonin reuptake inhibitors were shown to improve cardiovascular outcome. The most effective psychosocial treatment is multicomponent therapy that combines elements of cognitive behaviour therapy ("stress management") and changes in health behaviours, including the adoption of a regular exercise regimen. Gender-specific issues should probably be considered. The field of behavioural cardiology has accumulated a wealth of epidemiological, mechanistic and clinical knowledge that undoubtedly has furthered our understanding about the important role of psychosocial risk factors in patients with a heart disease.

Screening and testing for endocrine disruption in fish-biomarkers as "signposts," not "traffic lights," in risk assessment

Biomarkers are currently best used as mechanistic "signposts" rather than as "traffic lights" in the environmental risk assessment of endocrine-disrupting chemicals (EDCs). In field studies, biomarkers of exposure [e.g., vitellogenin (VTG) induction in male fish] are powerful tools for tracking single substances and mixtures of concern. Biomarkers also provide linkage between field and laboratory data, thereby playing an important role in directing the need for and design of fish chronic tests for EDCs. It is the adverse effect end points (e.g., altered development, growth, and/or reproduction) from such tests that are most valuable for calculating adverseNOEC (no observed effect concentration) or adverseEC10 (effective concentration for a 10% response) and subsequently deriving predicted no effect concentrations (PNECs). With current uncertainties, biomarkerNOEC or biomarkerEC10 data should not be used in isolation to derive PNECs. In the future, however, there may be scope to increasingly use biomarker data in environmental decision making, if plausible linkages can be made across levels of organization such that adverse outcomes might be envisaged relative to biomarker responses. For biomarkers to fulfil their potential, they should be mechanistically relevant and reproducible (as measured by interlaboratory comparisons of the same protocol). VTG is a good example of such a biomarker in that it provides an insight to the mode of action (estrogenicity) that is vital to fish reproductive health. Interlaboratory reproducibility data for VTG are also encouraging; recent comparisons (using the same immunoassay protocol) have provided coefficients of variation (CVs) of 38-55% (comparable to published CVs of 19-58% for fish survival and growth end points used in regulatory test guidelines). While concern over environmental xenoestrogens has led to the evaluation of reproductive biomarkers in fish, it must be remembered that many substances act via diverse mechanisms of action such that the environmental risk assessment for EDCs is a broad and complex issue. Also, biomarkers such as secondary sexual characteristics, gonadosomatic indices, plasma steroids, and gonadal histology have significant potential for guiding interspecies assessments of EDCs and designing fish chronic tests. To strengthen the utility of EDC biomarkers in fish, we need to establish a historical control database (also considering natural variability) to help differentiate between statistically detectable versus biologically significant responses. In conclusion, as research continues to develop a range of useful EDC biomarkers, environmental decision-making needs to move forward, and it is proposed that the "biomarkers as signposts" approach is a pragmatic way forward in the current risk assessment of EDCs.

Health risk appraisal in older people 1: are older people living alone an "at-risk" group?

BACKGROUND: In the UK, population screening for unmet need has failed to improve the health of older people. Attention is turning to interventions targeted at 'at-risk' groups. Living alone in later life is seen as a potential health risk, and older people living alone are thought to be an at-risk group worthy of further intervention. AIM: To explore the clinical significance of living alone and the epidemiology of lone status as an at-risk category, by investigating associations between lone status and health behaviours, health status, and service use, in non-disabled older people. Design of study: Secondary analysis of baseline data from a randomised controlled trial of health risk appraisal in older people. SETTING: Four group practices in suburban London. METHOD: Sixty per cent of 2641 community-dwelling non-disabled people aged 65 years and over registered at a practice agreed to participate in the study; 84% of these returned completed questionnaires. A third of this group, (n = 860, 33.1%) lived alone and two-thirds (n = 1741, 66.9%) lived with someone else. RESULTS: Those living alone were more likely to report fair or poor health, poor vision, difficulties in instrumental and basic activities of daily living, worse memory and mood, lower physical activity, poorer diet, worsening function, risk of social isolation, hazardous alcohol use, having no emergency carer, and multiple falls in the previous 12 months. After adjustment for age, sex, income, and educational attainment, living alone remained associated with multiple falls, functional impairment, poor diet, smoking status, risk of social isolation, and three self-reported chronic conditions: arthritis and/or rheumatism, glaucoma, and cataracts. CONCLUSION: Clinicians working with independently-living older people living alone should anticipate higher levels of disease and disability in these patients, and higher health and social risks, much of which will be due to older age, lower educational status, and female sex. Living alone itself appears to be associated with higher risks of falling, and constellations of pathologies, including visual loss and joint disorders. Targeted population screening using lone status may be useful in identifying older individuals at high risk of falling.

Sexual transmission of HIV according to viral load and antiretroviral therapy: systematic review and meta-analysis

OBJECTIVES: To synthesize the evidence on the risk of HIV transmission through unprotected sexual intercourse according to viral load and treatment with combination antiretroviral therapy (ART). DESIGN: Systematic review and meta-analysis. METHODS: We searched Medline, Embase and conference abstracts from 1996-2009. We included longitudinal studies of serodiscordant couples reporting on HIV transmission according to plasma viral load or use of ART and used random-effects Poisson regression models to obtain summary transmission rates [with 95% confidence intervals, (CI)]. If there were no transmission events we estimated an upper 97.5% confidence limit. RESULTS: We identified 11 cohorts reporting on 5021 heterosexual couples and 461 HIV-transmission events. The rate of transmission overall from ART-treated patients was 0.46 (95% CI 0.19-1.09) per 100 person-years, based on five events. The transmission rate from a seropositive partner with viral load below 400 copies/ml on ART, based on two studies, was zero with an upper 97.5% confidence limit of 1.27 per 100 person-years, and 0.16 (95% CI 0.02-1.13) per 100 person-years if not on ART, based on five studies and one event. There were insufficient data to calculate rates according to the presence or absence of sexually transmitted infections, condom use, or vaginal or anal intercourse. CONCLUSION: Studies of heterosexual discordant couples observed no transmission in patients treated with ART and with viral load below 400 copies/ml, but data were compatible with one transmission per 79 person-years. Further studies are needed to better define the risk of HIV transmission from patients on ART.

Toxicity and early treatment outcomes in low- and intermediate-risk prostate cancer managed by high-dose-rate brachytherapy as a monotherapy

PURPOSE: To determine the acute and late genitourinary (GU) and gastrointestinal (GI) toxicity and present short-term biochemical no evidence of disease (bNED) rates after high-dose-rate brachytherapy (HDR-B) monotherapy. METHODS AND MATERIALS: Between October 2003 and June 2006, 36 patients with low (28) and intermediate (8) risk prostate cancer (PCA) were treated by HDR-B monotherapy. All patients received one implant and four fractions of 9.5Gy within 48h for a total prescribed dose (PD) of 38Gy. Five patients received hormonal therapy (HT). Median age was 63.5 years and median followup was 3 years (range, 0.4-4 years). Toxicity was scored according to the CTCAE version 3.0. Biochemical failure was defined according to the Phoenix criteria. RESULTS: Acute and late Grade 3 GU toxicity was observed in 1 (3%) and 4 (11%) patients, respectively. Grade 3 GI toxicity was absent. The three- year bNED survival rate was 100%. The sexual preservation rate in patients without HT was 75%. Late Grade 3 GU toxicity was associated with the planning target volume (PTV) V(100) (% PTV receiving > or =100% of the PD; p=0.036), D(90) (dose delivered to 90% of the PTV; p=0.02), and the urethral V(120) (urethral volume receiving > or =120% of the PD; p=0.043). The urethral V(120) was associated with increased PTV V(100) (p<0.001) and D(90) (p=0.003). CONCLUSIONS: After HDR-B monotherapy, late Grade 3 GU toxicity is associated with the urethral V(120) and the V(100) and D(90) of the PTV. Decrease of the irradiated urethral volume may reduce the GU toxicity and potentially improve the therapeutic ratio of this treatment.

Social and regional variations in health status and health behaviours among Swiss young adults

OBJECTIVE To provide nationwide data on health status and health behaviours among young adults in Switzerland, and to illustrate social and regional variations. METHODS Data came from the Swiss Federal Surveys of Adolescents, conducted in 2010/11. The sample consisted of 32,424 young men and 1,467 young women. We used logistic regression models to examine patterns of social inequality for three measures of health status and three measures of health behaviour. RESULTS Among men, lower self-rated health, overweight and lower physical fitness levels were associated with lower educational and fewer financial resources. Patterns were similar among young women. Unfavourable self-rated health (odds ratio [OR]: men 0.83, women 0.75) and overweight (OR: men 0.84, women 0.85; p >0.05) were less common in the French- than in the German-language region. Low physical fitness was more common in the French- than in the German-language region. In both sexes, daily smoking was associated with fewer educational resources, and physical inactivity was associated with lower educational and fewer financial resources. Males from the Italian-language region were three times more likely to be physically inactive than their German-speaking counterparts (OR 2.95). Risk drinking was more widespread among males in the French- than in the German-speaking language region (OR 1.47). CONCLUSIONS Striking social and moderate regional differences exist in health status and health behaviours among young Swiss males and females. The current findings offer new empirical evidence on social determinants of health in Switzerland and suggest education, material resources and regional conditions to be addressed in public health practice and in more focused future research.

Effects of an educational patient safety campaign on patients' safety behaviours and adverse events

Rationale, aims and objectives  The study aims to investigate the effects of a patient safety advisory on patients' risk perceptions, perceived behavioural control, performance of safety behaviours and experience of adverse incidents. Method  Quasi-experimental intervention study with non-equivalent group comparison was used. Patients admitted to the surgical department of a Swiss large non-university hospital were included. Patients in the intervention group received a safety advisory at their first clinical encounter. Outcomes were assessed using a questionnaire at discharge. Odds ratios for control versus intervention group were calculated. Regression analysis was used to model the effects of the intervention and safety behaviours on the experience of safety incidents. Results  Two hundred eighteen patients in the control and 202 in the intervention group completed the survey (75 and 77% response rates, respectively). Patients in the intervention group were less likely to feel poorly informed about medical errors (OR = 0.55, P = 0.043). There were 73.1% in the intervention and 84.3% in the control group who underestimated the risk for infection (OR = 0.51, CI 0.31-0.84, P = 0.009). Perceived behavioural control was lower in the control group (meanCon  = 3.2, meanInt  = 3.5, P = 0.010). Performance of safety-related behaviours was unaffected by the intervention. Patients in the intervention group were less likely to experience any safety-related incident or unsafe situation (OR for intervention group = 0.57, CI 0.38-0.87, P = 0.009). There were no differences in concerns for errors during hospitalization. There were 96% of patients (intervention) who would recommend other patients to read the advisory. Conclusions  The results suggest that the safety advisory decreases experiences of adverse events and unsafe situations. It renders awareness and perceived behavioural control without increasing concerns for safety and can thus serve as a useful instrument for communication about safety between health care workers and patients.

Clustering of HCV coinfections on HIV phylogeny indicates domestic and sexual transmission of HCV

BACKGROUND: HCV coinfection remains a major cause of morbidity and mortality among HIV-infected individuals and its incidence has increased dramatically in HIV-infected men who have sex with men(MSM). METHODS: Hepatitis C virus (HCV) coinfection in the Swiss HIV Cohort Study(SHCS) was studied by combining clinical data with HIV-1 pol-sequences from the SHCS Drug Resistance Database(DRDB). We inferred maximum-likelihood phylogenetic trees, determined Swiss HIV-transmission pairs as monophyletic patient pairs, and then considered the distribution of HCV on those pairs. RESULTS: Among the 9748 patients in the SHCS-DRDB with known HCV status, 2768(28%) were HCV-positive. Focusing on subtype B(7644 patients), we identified 1555 potential HIV-1 transmission pairs. There, we found that, even after controlling for transmission group, calendar year, age and sex, the odds for an HCV coinfection were increased by an odds ratio (OR) of 3.2 [95% confidence interval (CI) 2.2, 4.7) if a patient clustered with another HCV-positive case. This strong association persisted if transmission groups of intravenous drug users (IDUs), MSMs and heterosexuals (HETs) were considered separately(in all cases OR >2). Finally we found that HCV incidence was increased by a hazard ratio of 2.1 (1.1, 3.8) for individuals paired with an HCV-positive partner. CONCLUSIONS: Patients whose HIV virus is closely related to the HIV virus of HIV/HCV-coinfected patients have a higher risk for carrying or acquiring HCV themselves. This indicates the occurrence of domestic and sexual HCV transmission and allows the identification of patients with a high HCV-infection risk.

Social Factors Associated with Readiness for Sexual Activity in Adolescents: A Population-Based Cohort Study

Various factors are associated with sexual activity in adolescence and it is important to identify those that promote healthy and adaptive romantic and sexual development. The objectives of this study were to describe rates of early sexual intercourse (before 16 years) and sexual readiness in adolescence and to assess the extent to which these were social patterned. We prospectively studied nearly 5,000 15-year-olds from the Avon Longitudinal Study of Parents and Children, a UK birth cohort. Between 2006 and 2008, female and male participants answered a computer assisted interview about romantic and sexual behaviors in the last year. Predictors of sexual intercourse and readiness for sexual intercourse were examined across a range of sociodemographic measures. Overall, 17.7 % (95 % CI 16.7 %, 18.9 %) of participants reported having had sexual intercourse in the last year, with more girls than boys reporting sexual experience (risk ratio 1.30, 95 % CI 1.15, 1.47). Of these, one-third of both male and female were classed as unready because they were unwilling, lacking in autonomy, felt regret or had not used contraception. There was strong evidence of social patterning for sexual activity with higher rates for young people from poorer homes, with lower social class, and with younger, less educated mothers. In contrast, among 860 young people who had had sexual intercourse, there was no clear evidence of associations between social factors and sexual readiness. The lack of social patterning in sexual readiness supports the provision of comprehensive education to develop life skills for adolescents across all social groups.

Higher Risk of Incident HCV-Coinfections in MSM with a Wide HIV Transmission Bottleneck

BACKGROUND  High-risk sexual behaviors have been suggested as drivers of the recent dramatic increase of sexually-transmitted HCV among HIV-infected men who have sex with men(MSM). METHODS  We assessed the association between the HIV-transmission-bottleneck and the prevalence and incidence of HCV-coinfections in HIV-infected MSM from the Swiss-HIV-Cohort-Study(SHCS). As a proxy for the width of the transmission bottleneck we used the fraction of ambiguous nucleotides in Genotypic-Resistance-Tests(GRTs) from recent HIV-infections. We defined a broad bottleneck as a fraction of ambiguous nucleotides exceeding a previously-established threshold(0.5%). RESULTS  From the SHCS, we identified 671 MSMs with available HCV-serologies and with a HIV-GRT sampled during recent infection. Of those, 161(24.0%) exhibited a broad HIV-transmission-bottleneck, 38(5.7%) had at least one positive HCV test, and 26(3.9%) had an incident HCV infection. Individuals with broad HIV-transmission bottlenecks exhibited a twofold-higher odds of having ever experienced an HCV coinfection(OR[95%CI]=2.2[1.1, 4.3]) and a threefold-higher hazard of an incident HCV infection(HR[95%CI]= 3.0[1.4, 6.6]) than individuals with narrow HIV-transmission-bottlenecks. CONCLUSIONS  Our results indicate that the currently occurring sexual spread of HCV is focused on those MSMs that are prone to exhibit broad HIV-transmission-bottlenecks. This is consistent with an important role of high-risk behavior and mucosal-barrier-impairment in the transmission of HCV among MSM.

Effect of Health Risk Assessment and Counselling on Health Behaviour and Survival in Older People: A Pragmatic Randomised Trial.

BACKGROUND Potentially avoidable risk factors continue to cause unnecessary disability and premature death in older people. Health risk assessment (HRA), a method successfully used in working-age populations, is a promising method for cost-effective health promotion and preventive care in older individuals, but the long-term effects of this approach are unknown. The objective of this study was to evaluate the effects of an innovative approach to HRA and counselling in older individuals for health behaviours, preventive care, and long-term survival. METHODS AND FINDINGS This study was a pragmatic, single-centre randomised controlled clinical trial in community-dwelling individuals aged 65 y or older registered with one of 19 primary care physician (PCP) practices in a mixed rural and urban area in Switzerland. From November 2000 to January 2002, 874 participants were randomly allocated to the intervention and 1,410 to usual care. The intervention consisted of HRA based on self-administered questionnaires and individualised computer-generated feedback reports, combined with nurse and PCP counselling over a 2-y period. Primary outcomes were health behaviours and preventive care use at 2 y and all-cause mortality at 8 y. At baseline, participants in the intervention group had a mean ± standard deviation of 6.9 ± 3.7 risk factors (including unfavourable health behaviours, health and functional impairments, and social risk factors) and 4.3 ± 1.8 deficits in recommended preventive care. At 2 y, favourable health behaviours and use of preventive care were more frequent in the intervention than in the control group (based on z-statistics from generalised estimating equation models). For example, 70% compared to 62% were physically active (odds ratio 1.43, 95% CI 1.16-1.77, p = 0.001), and 66% compared to 59% had influenza vaccinations in the past year (odds ratio 1.35, 95% CI 1.09-1.66, p = 0.005). At 8 y, based on an intention-to-treat analysis, the estimated proportion alive was 77.9% in the intervention and 72.8% in the control group, for an absolute mortality difference of 4.9% (95% CI 1.3%-8.5%, p = 0.009; based on z-test for risk difference). The hazard ratio of death comparing intervention with control was 0.79 (95% CI 0.66-0.94, p = 0.009; based on Wald test from Cox regression model), and the number needed to receive the intervention to prevent one death was 21 (95% CI 12-79). The main limitations of the study include the single-site study design, the use of a brief self-administered questionnaire for 2-y outcome data collection, the unavailability of other long-term outcome data (e.g., functional status, nursing home admissions), and the availability of long-term follow-up data on mortality for analysis only in 2014. CONCLUSIONS This is the first trial to our knowledge demonstrating that a collaborative care model of HRA in community-dwelling older people not only results in better health behaviours and increased use of recommended preventive care interventions, but also improves survival. The intervention tested in our study may serve as a model of how to implement a relatively low-cost but effective programme of disease prevention and health promotion in older individuals. TRIAL REGISTRATION International Standard Randomized Controlled Trial Number: ISRCTN 28458424.

Human 3β-hydroxysteroid dehydrogenase deficiency seems to affect fertility but may not harbor a tumor risk: lesson from an experiment of nature.

CONTEXT 3β-hydroxysteroid dehydrogenase deficiency (3βHSD) is a rare disorder of sexual development and steroidogenesis. There are two isozymes of 3βHSD, HSD3B1 and HSD3B2. Human mutations are known for the HSD3B2 gene which is expressed in the gonads and the adrenals. Little is known about testis histology, fertility and malignancy risk. OBJECTIVE To describe the molecular genetics, the steroid biochemistry, the (immuno-)histochemistry and the clinical implications of a loss-of-function HSD3B2 mutation. METHODS Biochemical, genetic and immunohistochemical investigations on human biomaterials. RESULTS A 46,XY boy presented at birth with severe undervirilization of the external genitalia. Steroid profiling showed low steroid production for mineralocorticoids, glucocorticoids and sex steroids with typical precursor metabolites for HSD3B2 deficiency. The genetic analysis of the HSD3B2 gene revealed a homozygous c.687del27 deletion. At pubertal age, he showed some virilization of the external genitalia and some sex steroid metabolites appeared likely through conversion of precursors secreted by the testis and converted by unaffected HSD3B1 in peripheral tissues. However, he also developed enlarged breasts through production of estrogens in the periphery. Testis histology in late puberty revealed primarily a Sertoli-cell-only pattern and only few tubules with arrested spermatogenesis, presence of few Leydig cells in stroma, but no neoplastic changes. CONCLUSIONS The testis with HSD3B2 deficiency due to the c.687del27 deletion does not express the defective protein. This patient is unlikely to be fertile and his risk for gonadal malignancy is low. Further studies are needed to obtain firm knowledge on malignancy risk for gonads harboring defects of androgen biosynthesis.

Depression predicts persistence of paranoia in clinical high-risk patients to psychosis: results of the EPOS project.

BACKGROUND The link between depression and paranoia has long been discussed in psychiatric literature. Because the causality of this association is difficult to study in patients with full-blown psychosis, we aimed to investigate how clinical depression relates to the presence and occurrence of paranoid symptoms in clinical high-risk (CHR) patients. METHODS In all, 245 young help-seeking CHR patients were assessed for suspiciousness and paranoid symptoms with the structured interview for prodromal syndromes at baseline, 9- and 18-month follow-up. At baseline, clinical diagnoses were assessed by the Structured Clinical Interview for DSM-IV, childhood adversities by the Trauma and Distress Scale, trait-like suspiciousness by the Schizotypal Personality Questionnaire, and anxiety and depressiveness by the Positive and Negative Syndrome Scale. RESULTS At baseline, 54.3 % of CHR patients reported at least moderate paranoid symptoms. At 9- and 18-month follow-ups, the corresponding figures were 28.3 and 24.4 %. Depressive, obsessive-compulsive and somatoform disorders, emotional and sexual abuse, and anxiety and suspiciousness associated with paranoid symptoms. In multivariate modelling, depressive and obsessive-compulsive disorders, sexual abuse, and anxiety predicted persistence of paranoid symptoms. CONCLUSION Depressive disorder was one of the major clinical factors predicting persistence of paranoid symptoms in CHR patients. In addition, obsessive-compulsive disorder, childhood sexual abuse, and anxiety associated with paranoia. Effective pharmacological and psychotherapeutic treatment of these disorders and anxiety may reduce paranoid symptoms in CHR patients.

Sexual health in hematopoietic stem cell transplant recipients

Hematopoietic stem cell transplantation (HSCT) plays a central role in patients with malignant and, increasingly, nonmalignant conditions. As the number of transplants increases and the survival rate improves, long-term complications are important to recognize and treat to maintain quality of life. Sexual dysfunction is a commonly described but relatively often underestimated complication after HSCT. Conditioning regimens, generalized or genital graft-versus-host disease, medications, and cardiovascular complications as well as psychosocial problems are known to contribute significantly to physical and psychological sexual dysfunction. Moreover, it is often a difficult topic for patients, their significant others, and health care providers to discuss. Early recognition and management of sexual dysfunction after HSCT can lead to improved quality of life and outcomes for patients and their partners. This review focuses on the risk factors for and treatment of sexual dysfunction after transplantation and provides guidance concerning how to approach and manage a patient with sexual dysfunction after HSCT.