Global control of sexually transmitted infections

Sexually transmitted infections other than HIV are important global health issues. They have, however, been neglected as a public-health priority and control efforts continue to fail. Sexually transmitted infections, by their nature, affect individuals, who are part of partnerships and larger sexual networks, and in turn populations. We propose a framework of individual, partnership, and population levels for examining the effects of sexually transmitted infections and interventions to control them. At the individual level we have a range of effective diagnostic tests, treatments, and vaccines. These options are unavailable or inaccessible in many resource-poor settings, where syndromic management remains the core intervention for individual case management. At the partnership level, partner notification and antenatal syphilis screening have the potential to prevent infection and re-infection. Interventions delivered to whole populations, or groups in whom the risks of infection and onward transmission are very high, have the greatest potential effect. Improvements to the infrastructure of treatment services can reduce the incidence of syphilis and gonorrhoea or urethritis. Strong evidence for the effectiveness of most other interventions on population-level outcomes is, however, scarce. Effective action requires a multifaceted approach including better basic epidemiological and surveillance data, high quality evidence about effectiveness of individual interventions and programmes, better methods to get effective interventions onto the policy agenda, and better advocacy and more commitment to get them implemented properly. We must not allow stigma, prejudice, and moral opposition to obstruct the goals of infectious disease control.

Cost effectiveness of home based population screening for Chlamydia trachomatis in the UK: economic evaluation of chlamydia screening studies (ClaSS) project

OBJECTIVE: To investigate the cost effectiveness of screening for Chlamydia trachomatis compared with a policy of no organised screening in the United Kingdom. DESIGN: Economic evaluation using a transmission dynamic mathematical model. SETTING: Central and southwest England. PARTICIPANTS: Hypothetical population of 50,000 men and women, in which all those aged 16-24 years were invited to be screened each year. MAIN OUTCOME MEASURES: Cost effectiveness based on major outcomes averted, defined as pelvic inflammatory disease, ectopic pregnancy, infertility, or neonatal complications. RESULTS: The incremental cost per major outcome averted for a programme of screening women only (assuming eight years of screening) was 22,300 pounds (33,000 euros; $45,000) compared with no organised screening. For a programme screening both men and women, the incremental cost effectiveness ratio was approximately 28,900 pounds. Pelvic inflammatory disease leading to hospital admission was the most frequently averted major outcome. The model was highly sensitive to the incidence of major outcomes and to uptake of screening. When both were increased the cost effectiveness ratio fell to 6200 pound per major outcome averted for screening women only. CONCLUSIONS: Proactive register based screening for chlamydia is not cost effective if the uptake of screening and incidence of complications are based on contemporary empirical studies, which show lower rates than commonly assumed. These data are relevant to discussions about the cost effectiveness of the opportunistic model of chlamydia screening being introduced in England.

Interactional behaviour as a marker for screening patients with environment-related complaints

BACKGROUND: Adequate assessment of symptoms of patients suffering from environmental illnesses requires appropriate procedures such as psychological and psychiatric diagnostics, medical screening and a thorough analysis of noxious environmental factors. The Basel pilot research project established a multi-methodological assessment procedure that meets these criteria. However, an exhaustive three-fold analysis is very costly in terms of both equipment and personnel, and hence the need for a heuristic approach and pre-screening persists. METHOD: The three-fold diagnostic approach was preceded by a structured psychodynamic interview; the findings were used to construct a new profile of the patient's interactional behaviour (IB) in conjunction with the interviewer's countertransference. The extent to which this new profile could predict the results of the multi-method assessment was then assessed. RESULTS: A low level of IB on the part of the patient significantly predicted the degree of stress and the extent of the psychiatric diagnosis, including personality disorders. A negative IB was associated with negative personality traits. Furthermore, a high level of IB implied more medical, but not more environmental, findings which could plausibly be related to the patient's complaints. CONCLUSIONS: Assessment of patients' IB in conjunction with one's own countertransference is very helpful as a preliminary heuristic approach and may lead to consequences for treatment and therapy. Therefore, the training provided for experts who deal with patients suffering from environment-related complaints should place more specific emphasis on assessing patients' behaviour and on incorporating information gathered from countertransference. Nevertheless, an interdisciplinary assessment including medical, psychological/psychiatric, and environmental expertise remains mandatory for adequate and satisfactory diagnosis of patients with environment-related complaints.

Hylan versus hyaluronic acid for osteoarthritis of the knee: a systematic review and meta-analysis

OBJECTIVE: To compare the effectiveness and safety of intraarticular high-molecular hylan with standard preparations of hyaluronic acids in osteoarthritis of the knee. METHODS: We performed a systematic review and meta-analysis of randomized controlled trials comparing hylan with a hyaluronic acid in patients with knee osteoarthritis. Trials were identified by systematic searches of Central, Medline, EMBase, Cinahl, the Food and Drug Administration, and Science Citation Index supplemented by hand searches of conference proceedings and reference lists (last update November 2006). Literature screening and data extraction were performed in duplicate. Effect sizes were calculated from differences in means of pain-related outcomes between treatment and control groups at the end of the trial, divided by the pooled standard deviation. Trials were combined using random-effects meta-analysis. RESULTS: Thirteen trials with a pooled total of 2,085 patients contributed to the meta-analysis. The pooled effect size was -0.27 (95% confidence interval [95% CI] -0.55, 0.01), favoring hylan, but between-trial heterogeneity was high (I(2) = 88%). Trials with blinded patients, adequate concealment of allocation, and an intent-to-treat analysis had pooled effect sizes near null. The meta-analyses on safety revealed an increased risk associated with hylan for any local adverse events (relative risk [RR] 1.91; 95% CI 1.04, 3.49; I(2) = 28%) and for flares (RR 2.04; 95% CI 1.18, 3.53; I(2) = 0%). CONCLUSION: Given the likely lack of a superior effectiveness of hylan over hyaluronic acids and the increased risk of local adverse events associated with hylan, we discourage the use of intraarticular hylan in patients with knee osteoarthritis in clinical research or practice.

The exchange of radiotherapy data as part of an electronic patient-referral system

PURPOSE: To describe the implementation and use of an electronic patient-referral system as an aid to the efficient referral of patients to a remote and specialized treatment center. METHODS AND MATERIALS: A system for the exchange of radiotherapy data between different commercial planning systems and a specially developed planning system for proton therapy has been developed through the use of the PAPYRUS diagnostic image standard as an intermediate format. To ensure the cooperation of the different TPS manufacturers, the number of data sets defined for transfer has been restricted to the three core data sets of CT, VOIs, and three-dimensional dose distributions. As a complement to the exchange of data, network-wide application-sharing (video-conferencing) technologies have been adopted to provide methods for the interactive discussion and assessment of treatments plans with one or more partner clinics. RESULTS: Through the use of evaluation plans based on the exchanged data, referring clinics can accurately assess the advantages offered by proton therapy on a patient-by-patient basis, while the practicality or otherwise of the proposed treatments can simultaneously be assessed by the proton therapy center. Such a system, along with the interactive capabilities provided by video-conferencing methods, has been found to be an efficient solution to the problem of patient assessment and selection at a specialized treatment center, and is a necessary first step toward the full electronic integration of such centers with their remotely situated referral centers.

Group B Streptococcus colonization in pregnancy: prevalence and prevention strategies of neonatal sepsis

Early onset neonatal sepsis due to Group B streptococci (GBS) is responsible for severe morbidity and mortality of newborns. While different preventive strategies to identify women at risk are being recommended, the optimal strategy depends on the incidence of GBS-sepsis and on the prevalence of anogenital GBS colonization. We therefore aimed to assess the Group B streptococci prevalence and its consequences on different prevention strategies. We analyzed 1316 pregnant women between March 2005 and September 2006 at our institution. The prevalence of GBS colonization was determined by selective cultures of anogenital smears. The presence of risk factors was analyzed. In addition, the direct costs of screening and intrapartum antibiotic prophylaxis were estimated for different preventive strategies. The prevalence of GBS colonization was 21%. Any maternal intrapartum risk factor was present in 37%. The direct costs of different prevention strategies have been estimated as follows: risk-based: 18,500 CHF/1000 live births, screening-based: 50,110 CHF/1000 live births, combined screening- and risk-based: 43,495/1000 live births. Strategies to prevent GBS-sepsis in newborn are necessary. With our colonization prevalence of 21%, and the intrapartum risk profile of women, the screening-based approach seems to be superior as compared to a risk-based approach.

Cystic fibrosis transmembrane conductance regulator mutations in azoospermic and oligospermic men and their partners

The objective of this study was to investigate the contribution of cystic fibrosis transmembrane conductance regulator (CFTR) to human infertility and to define screening and counselling procedures for couples asking for assisted reproduction treatment. Extended CFTR mutation screening was performed in 310 infertile men (25 with congenital absence of the vas deferens (CAVD), 116 with non-CAVD azoospermia, 169 with severe oligospermia), 70 female partners and 96 healthy controls. CFTR mutations were detected in the majority (68%) of CAVD patients and in significant proportions in azoospermic (31%) and oligospermic (22%) men. Carrier frequency among partners of infertile men was 16/70, exceeding that of controls (6/96) significantly (P = 0.0005). Thus, in 23% of infertile couples both partners were carriers, increasing the risk for their offspring to inherit two mutations to 25% or 50%. This study emphasizes the necessity to offer extended CFTR mutation screening and counselling not only to patients with CAVD but also to azoospermic and oligozoospermic men and their partners before undergoing assisted reproduction techniques. The identification of rare and/or mild mutations will not be a reason to abstain from parenthood, but will allow adequate treatment in children at risk for atypical or mild cystic fibrosis as soon as they develop any symptoms.

Changes in plasma lipids with psychosocial stress are related to hypertension status and the norepinephrine stress response

Hypertension is a known risk factor for cardiovascular disease. Hypertensive individuals show exaggerated norepinephrine (NE) reactivity to stress. Norepinephrine is a known lipolytic factor. It is unclear if, in hypertensive individuals, stress-induced increases in NE are linked with the elevations in stress-induced circulating lipid levels. Such a mechanism could have implications for atherosclerotic plaque formation. In a cross-sectional, quasi-experimentally controlled study, 22 hypertensive and 23 normotensive men (mean +/- SEM, 45 +/- 3 years) underwent an acute standardized psychosocial stress task combining public speaking and mental arithmetic in front of an audience. We measured plasma NE and the plasma lipid profile (total cholesterol [TC], low-density-lipoprotein cholesterol [LDL-C], high-density-lipoprotein cholesterol, and triglycerides) immediately before and after stress and at 20 and 60 minutes of recovery. All lipid levels were corrected for stress hemoconcentration. Compared with normotensives, hypertensives had greater TC (P = .030) and LDL-C (P = .037) stress responses. Independent of each other, mean arterial pressure (MAP) upon screening and immediate increase in NE predicted immediate stress change in TC (MAP: beta = .41, P = .003; NE: beta = .35, P = .010) and LDL-C (MAP: beta = .32, P = .024; NE: beta = .38, P = .008). Mean arterial pressure alone predicted triglycerides stress change (beta = .32, P = .043) independent of NE stress change, age, and BMI. The MAP-by-NE interaction independently predicted immediate stress change of high-density-lipoprotein cholesterol (beta = -.58, P < .001) and of LDL-C (beta = -.25, P < .08). We conclude that MAP and NE stress reactivity may elicit proatherogenic changes of plasma lipids in response to acute psychosocial stress, providing one mechanism by which stress might increase cardiovascular risk in hypertension.

Planung und Risikobewertung projektspezifischer Produktionsnetzwerke

Bei Einzel‐ und Kleinserienfertigung müssen sowohl langfristige Kooperationspartner als auch auftrags-spezifische, internationale Partner und Lieferanten in die Produktion komplexer Investitionsgüter einbezogen werden. Zunehmend sind kleine und mittlere Unternehmen (KMU) herausgefordert nicht nur technische Komponenten zu liefern, sondern die komplette Projektplanung zu realisieren. Im Forschungsprojekt „PIP“ soll ein Verfahren entwickelt werden, das gerade KMU des Maschinen- und Anlagenbaus bei der aufwandsmi-nimierten Partner- und Lieferantenauswahl sowie der Einschätzung möglicher Projektrisiken unterstützt. Der vorliegende Artikel beschreibt Rahmenbedingungen beim Aufbau projektspezifischer Produktionsnetzwerke sowie Lösungsansätze zu deren verbesserter Planung und Risikobewertung.

Subclinical hypothyroidism and cardiovascular risk: how to end the controversy

The indications for screening and TSH threshold levels for treatment of subclinical hypothyroidism have remained a clinical controversy for over 20 years. Subclinical thyroid dysfunction is a common finding in the growing population of older adults, occurring in 10–15% among those age 65 and older, and may contribute to multiple common problems of older age, including cardiovascular disease, muscular impairment, mood problems, and cognitive dysfunction (1). In 2004, both the U.S. Preventive Services Task Force (2) and a clinical consensus group of experts (3) concluded that the existing evidence about the association between subclinical hypothyroidism and cardiovascular risks, primarily cross-sectional or case-control studies (4), was insufficient. For example, a frequently cited analysis from the Rotterdam study found a cross-sectional association between subclinical hypothyroidism and atherosclerosis, as measured by abdominal aortic calcification (odds ratio, 1.7; 95% confidence interval [CI], 1.1–2.6) and prevalent myocardial infarction (MI) (odds ratio, 2.3; 95% CI, 1.3–4.0) (5). Conversely, the prospective part of this study included only 16 incident MIs; the hazard ratio (HR) for subclinical hypothyroidism was 2.50, with broad 95% CIs (0.70–9.10). Potential mechanisms for the associations with cardiovascular diseases among adults with subclinical hypothyroidism include elevated cholesterol levels, inflammatory markers, raised homocysteine, increased oxidative stress, insulin resistance, increased systemic vascular resistance, arterial stiffness, altered endothelial function, and activation of thrombosis and hypercoagulability that have all been reported to be associated with subclinical hypothyroidism (1, 6).

Repeat chlamydia screening among adolescents: cohort study in a school-based programme in New Orleans

OBJECTIVES To describe uptake of chlamydia screening, determine rates of repeated yearly screening and investigate determinants of repeated participation in an organised school-based screening programme. METHODS The authors analysed data from 1995 to 2005 from female and male students in up to 13 schools in New Orleans, Louisiana, USA. The authors calculated proportions of students tested among all enrolled students and among those with parental consent and the percentage of positive chlamydia tests in each school year. The authors used random effects logistic regression to examine the effect of past screening history on subsequent participation. RESULTS 35 041 students were registered for at least one school year. Overall coverage was >30% in all school years. Among all students registered for 4 years, 10.6% (95% CI 9.3% to 12.0%) of women and 12.7% (95% CI 11.2% to 14.2%) of men had a test every year. Among students with parental consent for 4 years, 49.3% (95% CI 44.6% to 54.1%) of women and 59.3% (95% CI 54.5% to 64.0%) of men had a test every year. Among students registered for 2 or more years, those with a previous positive chlamydia test were less likely to have a subsequent test (female adjusted OR 0.77, 95% CI 0.67 to 0.88 and male adjusted OR 0.84, 95% CI 0.69 to 1.02). Chlamydia positivity increased over time. CONCLUSIONS High levels of uptake can be achieved in school-based chlamydia screening programmes, but repeated yearly screening is difficult to sustain over time.

Reinfection by untreated partners of people treated for Chlamydia trachomatis and Neisseria gonorrhoeae: mathematical modelling study

OBJECTIVES Reinfection after treatment for Chlamydia trachomatis or Neisseria gonorrhoeae reduces the effect of control interventions. We explored the impact of delays in treatment of current partners on the expected probability of reinfection of index cases using a mathematical model. METHODS We used previously reported parameter distributions to calculate the probability that index cases would be reinfected by their untreated partners. We then assumed different delays between index case and partner treatment to calculate the probabilities of reinfection. RESULTS In the absence of partner treatment, the medians of the expected reinfection probabilities are 19.4% (IQR 9.2-31.6%) for C trachomatis and 12.5% (IQR 5.6-22.2%) for N gonorrhoeae. If all current partners receive treatment 3 days after the index case, the expected reinfection probabilities are 4.2% (IQR 2.1-6.9%) for C trachomatis and 5.5% (IQR 2.6-9.5%) for N gonorrhoeae. CONCLUSIONS Quicker partner referral and treatment can substantially reduce reinfection rates for C trachomatis and N gonorrhoeae by untreated partners. The formula we used to calculate reinfection rates can be used to inform the design of randomised controlled trials of novel partner notification technologies like accelerated partner therapy.

Expression, purification, and projection structure by single particle electron microscopy of functional human TRPM4 heterologously expressed in Xenopus laevis oocytes

Despite efforts implicating the cationic channel transient receptor potential melastatin member 4 (TRPM4) to cardiac, nervous, and immunological pathologies, little is known about its structure and function. In this study, we optimized the requirements for purification and extraction of functional human TRPM4 protein and investigated its supra-molecular assembly. We selected the Xenopus laevis oocyte expression system because it lacks endogenous TRPM4 expression, it is known to overexpress functional human membrane channels, can be used for structure-function analysis within the same system, and is easily scaled to improve yield and develop moderate throughput capabilities through the use of robotics. Negative-stain electron microscopy (EM) revealed various sized low-resolution particles. Single particle analysis identified the majority of the projections represented the monomeric form with additional oligomeric structures potentially characterized as tetramers. Two-electrode voltage clamp electrophysiology demonstrated that human TRPM4 is functionally expressed at the oocyte plasma membrane. This study opens the door for medium-throughput screening and structure-function determination of this important therapeutically relevant target.

Social control and smoking: Examining the moderating effects of different dimensions of relationship quality

A common form of social regulation of an individual’s health behavior is social control. The contextual model of social control assumes that higher relationship quality goes along with more beneficial effects of social control on health behavior. This study examined potential differential moderating effects of different dimensions of relationship quality on the associations between positive and negative social control and smoking behavior and hiding smoking. The sample consisted of 144 smokers (n = 72 women; mean age = 31.78, SD = 10.04) with a nonsmoking partner. Positive and negative social control, dimensions of relationship quality consensus, cohesion and satisfaction, numbers of cigarettes smoked (NCS), hiding smoking (HS), and control variables were assessed at baseline. Four weeks later NCS and HS were assessed again. Only for smokers with high consensus, but not cohesion and satisfaction, a negative association between positive control and NCS emerged. Moreover, smokers with high consensus tended to report more HS when being positively and negatively socially controlled. This also emerged for cohesion and positive control. Satisfaction with the relationship did not display any interaction effects. This study’s results emphasize the importance of differentiating not only between positive and negative social control but also between different dimensions of relationship quality in order to gain a comprehensive understanding of the dynamics in romantic dyads with regard to social regulation of behavioral change.

Who’s to blame? How narcissists and ex-partners of narcissists make sense of romantic breakup

Objective: past research has shown relationship problems associated with narcissists’ excessive self-centeredness and lacking concern for others. Using romantic relationships as opportunities to self-enhance rather than caring about intimacy, narcissists are sensitive to shortcomings in their partners and quick to withdraw investment once relationships turn out to be less than perfect. Our research aimed to reveal whether narcissists are aware of their destructive relationship behavior or tend to put the blame for a failed relationship on their ex-partners. Conversely, do ex-partners of narcissists take the blame and feel responsible for the breakup or walk away convinced their narcissistic ex-partners’ behavior was just too unbearable? Method: 120 participants (19-59 yrs) who reported a recent romantic breakup completed a battery of questionnaires online, including measures of narcissism and self-esteem, as well as newly created scales assessing attributions for breakup. In addition to self-reports, participants retrospectively rated their ex-partners on adapted versions of the same measures. Results: narcissists made attributions to lacking relationship investment mostly in themselves and to a lesser extent in their partners. However, this pattern was reversed when self-esteem was controlled, with attributions to partner shortcomings outnumbering aspects of own destructive behavior. Narcissism perceived in the ex-partner was related to reports of lacking investment in oneself as well as the ex-partner, but controlling for self-esteem reduced the number of attributions to own shortcomings. Conclusion: our analyses revealed that narcissists do show some awareness of their contribution to a failed relationship, although controlling for self-esteem increased their blame of the ex-partner. In contrast, associations between perceived partner-narcissism and aspects of own lacking relationship investment became fewer when self-esteem was controlled for.